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[(t)-6.9 (ar)1.3 (g)14.1 (e)15.8 (t)-7.4 (s f)24.4 (or the de)18.2 (v)26.4 (e)30.3 (lopment of c)-5.9 (anc)12.2 (er v)24 (ac)13.1 (cine)13 (s and )-0.7 (v)24 (ar)-15.9 (ious )]TJ
0.156 Tw 0 -1.412 Td
[(t)-27.9 (ype)12.8 (s of v)23.9 (ac)13.1 (cine)13 (s t)13.6 (e)12.8 (s)9 (t)13.6 (ed in c)15.6 (linic)-5.3 (al t)-10.8 (r)-15.8 (i)21.2 (als alon)14.9 (g w)-7.7 (it)0.7 (h f)-12.2 (ut)-14.8 (ur)9.5 (e )]TJ
0 Tw 0 -1.412 Td
[(s)9 (t)-10.8 (r)5.7 (a)20 (t)13.6 (e)7.4 (gie)13.1 (s in t)0.8 (his f)-32.3 (ie)30.6 (ld)-1 (.)]TJ
/TT2 1 Tf
0.02 Tc 11 0 0 11 65.1969 643.7025 Tm
[(T)62 (umor Ant)5.7 (i)1.1 (gens f)7 (or C)-5.1 (anc)9.6 (er V)42 (ac)10.2 (cine)]TJ
/TT1 1 Tf
0 Tc 0.001 Tw 8.5 0 0 8.5 65.1969 625.7025 Tm
[(T)-17.7 (her)9.8 (e ar)9.5 (e mainl)14.3 (y f)24.4 (our c)-5.8 (a)19.9 (t)13.6 (e)7.5 (g)13.2 (or)-15.7 (ie)13 (s of t)-14.7 (umor ant)-10.8 (i)22.1 (g)14.2 (en t)-6.9 (ar)1.3 (g)14.1 (e)15.8 (t)-7.4 (s f)24.4 (or )]TJ
-0.02 Tw 0 -1.412 Td
[(the de)18.2 (v)26.4 (e)30.4 (lopment )0.6 (of c)-5.8 (anc)12.1 (er v)24 (ac)13.1 (cine)10.9 (. Out of t)0.5 (hem, )0.6 (neoant)-10.5 (i)22.2 (g)14.1 (ens )]TJ
0.208 Tw 0 -1.412 Td
[(ar)9.5 (e the mos)9.3 (t po)14.2 (t)13.6 (ent)-10.6 (i)21.2 (al t)-6.9 (ar)1.2 (g)14.2 (e)15.7 (t)-7.3 (s f)24.4 (or t)0.5 (her)5.8 (apeut)-10.9 (ic c)-5.9 (anc)12.2 (er v)24 (ac)]TJ
0 Tw (-)Tj
0 -1.412 Td
[(cine)13.1 (s)-4.7 (. Her)9.7 (e)10.9 (, w)26.6 (e de)12.7 (scr)-15.6 (ibe e)10.6 (ac)15.6 (h ent)-10.6 (it)-27.7 (y br)-15.7 (ie)23.2 (f)-55.6 (l)13.8 (y)48 (.)]TJ
/TT2 1 Tf
0.02 Tc 9 0 0 9 65.1969 565.7025 Tm
[(T)62 (umor-)-1.3 (A)-11.7 (s)4.4 (soci)7.4 (a)4.6 (t)7.2 (ed Ant)5.7 (i)1 (gens)]TJ
/TT1 1 Tf
-0.005 Tc 0.149 Tw 8.5 0 0 8.5 65.1969 553.7025 Tm
[(T)85.8 (umor-)1.3 (as)11.4 (soci)21.2 (a)19.9 (t)13.6 (ed ant)-10.8 (i)22.2 (g)14.2 (ens \()15 (T)37 (A)-43.1 (A)-15.8 (s\) ar)9.6 (e se)30.3 (lf)20.5 (-)1.3 (ant)-10.8 (i)22.2 (g)14.1 (ens tha)19.9 (t ar)9.6 (e)-4.9 ( )]TJ
0.289 Tw 0 -1.412 Td
[(abnor)-15.8 (mall)13.8 (y e)11.8 (xpr)9.6 (e)12.8 (s)11.4 (sed in t)-14.7 (umor c)12.2 (e)30.4 (lls and t)15.5 (o some e)11.8 (xt)13.7 (ent)-5 ( )]TJ
0.017 Tw 0 -1.412 Td
[(e)11.8 (xpr)9.6 (e)12.8 (s)11.4 (sed )0.5 (in )0.5 (nor)-15.8 (mal c)12.2 (e)30.4 (lls )0.5 (t)15.6 (oo)7.4 (. )0.5 (T)61.4 (-c)12.2 (e)30.3 (lls r)9.6 (ec)13.6 (o)9.9 (gni)2.7 (z)8.2 (e )0.5 (the)12.8 (se )0.5 (T)37 (A)-43.2 (A)-15.8 (s )0.5 (as)-4.8 ( )]TJ
0.086 Tw 0 -1.412 Td
[(se)30.4 (lf)20.5 (-)1.3 (ant)-10.8 (i)22.2 (g)14.2 (ens and b)20.4 (y t)0.5 (he ac)-13.2 (t)-10.8 (i)14.4 (v)23.9 (a)19.9 (t)-10.7 (ion of c)12.2 (ent)-10.8 (r)5.7 (al and per)-15.8 (ipher)5.7 (al)-4.8 ( )]TJ
0.155 Tw 0 -1.412 Td
[(immune t)15.6 (oler)5.7 (anc)12.2 (e mec)15.6 (hanisms)-4.7 (, t)0.5 (he)12.8 (se ar)9.6 (e de)30.4 (le)15.7 (t)13.6 (ed fr)8.6 (om the)-4.9 ( )]TJ
0.051 Tw 0 -1.412 Td
[(immune )0.5 (sy)17.2 (s)9 (t)13.6 (em. )0.5 (F)12.9 (or )0.5 (this )0.5 (r)9.6 (e)10.3 (ason, )0.5 (c)-5.9 (anc)12.3 (er )0.5 (v)23.9 (ac)13.2 (cine)12.8 (s )0.5 (usin)14.6 (g the)12.8 (se)-4.9 ( )]TJ
0.047 Tw 0 -1.412 Td
[(ant)-10.8 (i)22.1 (g)14.2 (ens mus)9 (t be po)14.3 (t)13.6 (ent enou)20.9 (g)-1.4 (h t)15.6 (o br)9.7 (e)10.3 (ak immune t)15.6 (oler)5.7 (anc)12.2 (e)10.9 (.)-4.9 ( )]TJ
0.061 Tw 0 -1.412 Td
[(T)79 (ar)1.3 (g)14.2 (e)15.7 (t)-10.8 (in)14.7 (g T)37 (A)-43.1 (A)-15.8 (s in t)0.5 (he de)18.2 (v)26.3 (e)30.4 (lopment of v)23.9 (ac)13.2 (cine me)15.7 (t w)-7.7 (it)0.5 (h lim)]TJ
0 Tc 0 Tw 27.335 0 Td
(-)Tj
-0.005 Tc 0.046 Tw -27.335 -1.412 Td
[(it)13.6 (ed suc)13.1 (c)12.2 (e)12.9 (s)11.4 (s as the)12.8 (se ar)9.6 (e nor)-15.8 (mal hos)9 (t pr)8.7 (o)14.2 (t)13.7 (eins and de)12.8 (s)9 (t)-10.8 (r)8.6 (o)25.5 (y)25.6 (ed)-5.2 ( )]TJ
0.244 Tw 0 -1.412 Td
[(b)20.4 (y c)12.2 (ent)-10.8 (r)5.7 (al and per)-15.8 (ipher)5.7 (al t)15.6 (oler)5.7 (anc)12.2 (e)10.9 (.)]TJ
0 Tc 0 Tw 4.913 0 0 4.913 210.7334 448.6775 Tm
(2)Tj
-0.005 Tc 0.244 Tw 8.5 0 0 8.5 213.5539 445.7025 Tm
[( V)57.5 (ar)-15.8 (ious aut)15.6 (oimmune)-4.9 ( )]TJ
0.281 Tw -17.454 -1.412 Td
[(t)15.6 (o)29.9 (xicit)-10.8 (ie)12.8 (s suc)15.6 (h as hepa)20 (t)-10.8 (it)-10.8 (is)-4.7 (, r)9.6 (enal im)20.7 (pair)-15.8 (ment)-10.8 (, c)13.6 (olit)-10.8 (is)-4.7 (, and)-5.2 ( )]TJ
-0.007 Tw 0 -1.412 Td
[(r)9.6 (e)12.8 (s)15.4 (pir)5.7 (a)19.9 (t)15.6 (or)-31.9 (y f)16.1 (ailur)9.6 (e also oc)13.1 (c)-9.7 (ur)-15.8 (r)9.6 (ed due t)15.6 (o t)-6.9 (ar)1.3 (g)14.2 (e)15.7 (t)-10.8 (in)14.7 (g the)12.8 (se T)37 (A)-43.1 (A)-15.8 (s)-4.7 (.)]TJ
0 Tc 0 Tw 4.913 0 0 4.913 298.1943 424.6775 Tm
(3)Tj
8.5 0 0 8.5 301.0394 421.7025 Tm
( )Tj
-0.005 Tc -0.045 Tw -27.746 -1.412 Td
[(S)1.6 (e)18.2 (v)26.3 (er)5.7 (al T)37 (A)-43.1 (A)-15.8 (s lik)30.1 (e)23.1 (; C)-5.4 (D)-18.4 (-19 e)11.8 (xpr)9.6 (e)12.8 (s)11.4 (sed on B c)12.2 (e)30.4 (ll mali)22.2 (gnancie)12.8 (s and)-5.2 ( )]TJ
-0.039 Tw 0 -1.412 Td
[(ER)-23.6 (BB)-19.5 (-2 on br)9.6 (e)10.4 (as)8.9 (t c)-5.9 (anc)12.2 (er c)12.2 (e)30.4 (ll ar)9.6 (e po)14.3 (t)13.6 (ent)-10.8 (i)21.2 (al t)-6.9 (ar)1.3 (g)14.2 (e)15.7 (t)-7.4 (s of C)-13.7 (AR)38.4 (-)61.4 (T c)12.2 (e)30.3 (ll)-4.8 ( )]TJ
0.057 Tw 0 -1.412 Td
[(ther)5.7 (ap)22.8 (y )0.5 (le)10.3 (ads )0.6 (t)15.5 (o )0.6 (on )0.5 (t)-6.9 (ar)1.3 (g)14.1 (e)15.8 (t )0.6 (but )0.5 (of)-14.1 (f )0.6 (t)-14.7 (umor )0.5 (side )0.5 (e)23.1 (f)-14.2 (f)24.4 (ec)-13.2 (t)-7.3 (s )0.5 (bec)-5.9 (ause)-4.9 ( )]TJ
-0.01 Tw 0 -1.412 Td
[(the)12.8 (se T)37 (A)-43.1 (A)-15.8 (s ar)9.6 (e also e)11.9 (xpr)9.6 (e)12.9 (s)11.4 (sed on nor)-15.7 (mal c)12.2 (e)30.4 (lls)-4.7 (.)]TJ
0 Tc 0 Tw 4.913 0 0 4.913 242.648 376.6775 Tm
(4)Tj
0.574 0 Td
(-)Tj
0.406 0 Td
(6)Tj
-0.005 Tc -0.01 Tw 8.5 0 0 8.5 250.2844 373.7025 Tm
[( It has sho)25.5 (wn)-4.9 ( )]TJ
0.067 Tw -21.775 -1.412 Td
[(a si)22.1 (gnif)-32.8 (ic)-5.8 (ant r)9.6 (e)12.8 (s)15.4 (ponse in some ALL, but t)0.5 (her)9.6 (e had been hu)20.9 (g)14.1 (e)-4.8 ( )]TJ
-0.029 Tw 0 -1.412 Td
[(c)15.6 (hallen)14.7 (g)14.2 (e)12.8 (s t)15.6 (o t)-10.7 (r)9.6 (e)10.3 (a)20 (t solid t)-14.7 (umors due t)15.6 (o lac)15.6 (k of suit)-6.9 (able T)37 (A)-43.2 (A)-15.8 (s)-4.6 (.)]TJ
0 Tc 0 Tw 4.913 0 0 4.913 294.2493 352.6775 Tm
(4)Tj
0.574 0 Td
(,)Tj
0.229 0 Td
(5)Tj
8.5 0 0 8.5 301.0394 349.7025 Tm
( )Tj
-0.005 Tc 0.192 Tw -27.746 -1.412 Td
[(T)-17.7 (he r)9.6 (epor)-23.1 (t)13.6 (ed o)25.5 (v)26.4 (er)5.7 (all ob)24.8 (jec)-13.2 (t)-10.8 (i)14.3 (v)26.4 (e r)9.6 (e)12.8 (s)15.4 (ponse r)5.7 (a)20 (t)13.6 (e)12.8 (s of C)-13.8 (AR)38.4 (-)61.3 (T c)12.2 (e)30.4 (ll)-4.9 ( )]TJ
0 Tw 0 -1.412 Td
[(ther)5.7 (ap)22.8 (y f)24.4 (or solid t)-14.7 (umors ar)9.6 (e s)9 (t)-10.8 (ill lo)25.5 (w)45 (.)]TJ
0 Tc 4.913 0 0 4.913 207.4625 328.6775 Tm
(7)Tj
0.574 0 Td
(,)Tj
0.229 0 Td
(8)Tj
/TT2 1 Tf
0.02 Tc 9 0 0 9 65.1969 301.7025 Tm
[(C)-5.1 (anc)9.6 (er G)-2.4 (er)1.1 (mline Ant)5.8 (i)1 (gens)]TJ
/TT1 1 Tf
0 Tc 0.378 Tw 8.5 0 0 8.5 65.1969 289.7025 Tm
[(C)-10.3 (anc)12.2 (er g)14.1 (er)-15.6 (mline )1 (ant)-10.8 (i)22.2 (g)14.1 (ens)-4.5 (, )0.5 (also c)-5.9 (alled )0.5 (c)-5.9 (anc)12.2 (er/)-5.9 (t)13.6 (e)12.8 (s)9 (t)-10.8 (is )0.7 (ant)-10.8 (i)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.207 Tw -27.335 -1.412 Td
[(g)14.2 (ens \(C)-28.5 (T)37 (A)-15.7 (s\), ar)9.6 (e immuno)10.5 (g)14.1 (enic pr)8.6 (o)14.3 (t)13.6 (eins enc)13.8 (oded b)20.4 (y g)14.1 (ene)13 (s )]TJ
0.312 Tw 0 -1.412 Td
[(tha)20 (t ar)9.5 (e nor)-15.7 (mall)13.8 (y e)11.8 (xpr)9.3 (e)12.8 (s)11.4 (sed in g)9.8 (ame)15.9 (t)13.6 (e)12.8 (s and t)-10.8 (r)8.6 (ophoblas)9.2 (t )]TJ
0.089 Tw 0 -1.412 Td
[(and also e)11.9 (xpr)9.3 (e)12.8 (s)11.4 (sed in v)24 (ar)-15.9 (ious )0.5 (c)-5.9 (anc)12.2 (er c)12.2 (e)30.4 (ll line)13.2 (s suc)15.7 (h as me)30.6 (l)]TJ
0 Tw 27.335 0 Td
(-)Tj
-0.032 Tw -27.335 -1.412 Td
[(anoma and c)-5.9 (ar)13.5 (cinomas of the bladder)53.2 (, lun)14.8 (g)1 (, and li)14.5 (v)26.4 (er)53.7 (.)]TJ
0 Tw 4.913 0 0 4.913 270.4922 244.6775 Tm
(9)Tj
(,)Tj
(10)Tj
-0.032 Tw 8.5 0 0 8.5 280.1671 241.7025 Tm
[( T)-17.7 (he)18.3 (y )]TJ
0.209 Tw -25.291 -1.412 Td
[(ar)9.5 (e )0.6 (bein)14.9 (g e)18.2 (v)24 (alua)19.9 (t)13.7 (ed as )0.6 (t)-6.9 (ar)1.2 (g)14.2 (e)15.7 (t)-7.3 (s )0.6 (f)24.4 (or ther)5.9 (apeut)-11 (ic )0.7 (c)-5.9 (anc)12.2 (er v)23.9 (ac)]TJ
0 Tw (-)Tj
0.122 Tw 0 -1.412 Td
[(cine)13.1 (s)-4.7 (. )0.5 (Me)30.3 (lanoma-)1.3 (as)11.3 (soci)21.5 (a)20 (t)13.6 (ed ant)-10.8 (i)22.2 (g)14.2 (en )0.5 (3 \(M)-17.8 (A)30.6 (GE)4.9 (-)9.1 (A3\) is )0.8 (a t)-27.9 (ype )]TJ
0.202 Tw 0 -1.412 Td
[(of C)-28.4 (T)37 (A enc)13.7 (oded b)20.4 (y t)0.5 (he M)-17.6 (A)30.6 (GE)4.8 (-)9.1 (A g)14.1 (ene f)16.1 (amil)14.2 (y e)11.8 (xpr)9.3 (e)12.8 (s)11.4 (sed in )]TJ
0.141 Tw 0 -1.412 Td
[(c)13.7 (ommon )0.7 (epit)0.6 (he)30.4 (li)21.4 (al mali)22.5 (gnancie)13 (s inc)15.9 (ludin)14.7 (g e)12.8 (sopha)20.2 (g)14.1 (e)10.4 (al c)-5.9 (an)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.09 Tw -27.335 -1.412 Td
[(c)12.2 (er and me)30.6 (lanoma)-7.4 (. Mor)1.4 (g)9.7 (an e)15.8 (t al t)-10.8 (r)9.6 (e)10.4 (a)20 (t)13.6 (ed nine )0.5 (pa)19.8 (t)-10.8 (ient)-7 (s w)-7.7 (it)0.6 (h )]TJ
0.082 Tw 0 -1.412 Td
[(adop)13.8 (t)-10.7 (i)14.3 (v)26.4 (e )0.5 (c)12.2 (e)30.4 (ll )0.7 (ther)5.7 (ap)22.7 (y )0.6 (usin)15 (g aut)15.4 (olo)9.8 (g)13.2 (ous )0.6 (ant)-10.8 (i)4.6 (-M)-17.8 (A)30.6 (GE)4.8 (-)9.2 (A3 T c)12.2 (e)30.4 (ll )]TJ
0.061 Tw 0 -1.412 Td
[(r)9.6 (ec)12.3 (ep)14.2 (t)15.5 (or-en)14.7 (gineer)10.1 (ed T)61.4 (-c)12.1 (e)30.4 (lls)-4.3 (, but se)18.3 (v)26.4 (er)9.7 (e neur)8.7 (olo)10.2 (gic)-5.7 (al t)15.6 (o)29.9 (xicit)-27.7 (y )]TJ
0 Tw 0 -1.412 Td
[(and de)9.9 (a)20 (th led t)15.7 (o f)16.2 (ailur)9.9 (e of t)0.6 (his appr)8.7 (oac)15.7 (h.)]TJ
4.913 0 0 4.913 222.368 148.6775 Tm
(11)Tj
/TT2 1 Tf
0.02 Tc 9 0 0 9 65.1969 121.7025 Tm
[(Onc)11.6 (ogenic V)-5.3 (ir)8.9 (al Ant)5.7 (i)1 (gen)]TJ
/TT1 1 Tf
0 Tc -0.08 Tw 8.5 0 0 8.5 65.1969 109.7025 Tm
[(V)3.4 (ir)-19.5 (use)12.9 (s mos)9.4 (t c)13.7 (ommonl)14.5 (y as)11.4 (soci)21.5 (a)19.9 (t)13.7 (ed w)-7.7 (it)0.6 (h human mali)22.5 (gnancie)13 (s )]TJ
-0.021 Tw 0 -1.412 Td
[(ar)9.5 (e Eps)8.8 (t)13.6 (ein\226Bar)-15.8 (r v)-9.8 (ir)-19.5 (us)-4.7 (, HB)22.8 (V)81.5 (, HC)-28.5 (V)81.5 (, HPV)81.5 (, K)2.1 (aposi)19.8 (\222)13.7 (s s)2.2 (ar)13.4 (c)13.7 (oma her)]TJ
0 Tw (-)Tj
0.028 Tw 0 -1.412 Td
[(pe)12.7 (sv)-9.8 (ir)-19.5 (us)-4.7 (, and human T c)12.2 (e)30.4 (ll )0.6 (l)13.8 (ym)20.9 (pho)14.3 (t)-10.8 (r)8.6 (opic v)-9.8 (ir)-19.5 (us)2.6 (-1. T)-17.7 (he de)18 (v)26.4 (e)30.4 (l)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.011 Tw -27.335 -1.412 Td
[(opment of pr)8.5 (oph)27.3 (y)14.3 (lac)-13.1 (t)-10.7 (ic v)23.9 (ac)13.1 (cine)13.1 (s a)20 (g)9.8 (ains)9.1 (t t)0.5 (he)12.8 (se v)-9.8 (ir)5.9 (al)3.5 (-enc)13.7 (oded )]TJ
0.429 Tw 0 -1.412 Td
[(ant)-10.8 (i)22.2 (g)14.1 (ens )0.6 (e)23.1 (f)-14.2 (f)24.4 (ec)-13.1 (t)-10.8 (i)14.4 (v)26.4 (e)30.4 (l)13.8 (y r)9.7 (educ)12 (e)12.8 (s the r)-15.8 (is)25.8 (k of v)-9.7 (ir)-19.5 (us)2.6 (-)1.3 (as)11.4 (soci)21.5 (a)19.9 (t)13.6 (ed )]TJ
0 Tw 0 -1.412 Td
[(c)-5.9 (anc)12.2 (er)53.7 (.)]TJ
-0.039 Tw 30.748 80.471 Td
[(HC)19.9 (C due t)15.6 (o c)15.6 (hr)8.7 (onic HB)22.8 (V inf)24.7 (ec)-13.1 (t)-10.8 (ion has been e)23 (f)-14.1 (f)24.4 (ec)-13.1 (t)-10.8 (i)14.4 (v)26.4 (e)30.4 (l)13.8 (y pr)9.5 (e)]TJ
0 Tw 26.001 0 Td
(-)Tj
0.123 Tw -27.335 -1.426 Td
[(v)26.4 (ent)13.8 (ed b)20.4 (y )0.6 (HB)22.8 (V v)24 (ac)13.1 (cina)20.2 (t)-10.8 (ion. )0.8 (T)79 (ai)15.8 (w)26 (an is )0.8 (a h)27.4 (yper)9.7 (endemic )0.9 (ar)9.5 (e)10.4 (a )]TJ
0.02 Tw 0 -1.426 Td
[(f)24.4 (or )0.5 (HB)22.9 (V )0.5 (inf)24.6 (ec)-13 (t)-10.8 (ion, )0.9 (wher)9.9 (e )0.7 (the )0.7 (ma)30.4 (jor)-15.7 (it)-27.7 (y )0.7 (of )0.6 (adult HC)19.8 (C )0.5 (c)-5.9 (ase)13 (s )0.7 (ar)9.5 (e )]TJ
0.045 Tw 0 -1.426 Td
[(due t)15.6 (o HB)22.9 (V inf)24.6 (ec)-13.1 (t)-10.8 (ion. HC)-28.5 (V inf)24.6 (ec)-13 (t)-10.8 (ion also pla)27.3 (y)17.3 (s an im)21 (por)-23.2 (t)-6.8 (ant )]TJ
-0.001 Tw 0 -1.426 Td
[(r)8.6 (ole in t)0.5 (he pr)9.4 (e)18.2 (v)24 (alenc)12.3 (e of HC)19.9 (C in dif)-14 (f)24.4 (er)9.7 (ent g)14.2 (eo)10 (g)-10.3 (r)5.7 (aphic ar)9.6 (e)10.3 (as of )]TJ
0 Tw 0 -1.426 Td
[(T)79 (ai)15.7 (w)26 (an.)]TJ
4.913 0 0 4.913 344.7343 676.0687 Tm
(12)Tj
0.015 Tw 8.5 0 0 8.5 350.4246 673.0937 Tm
[( T)-17.7 (her)9.8 (e w)26 (as a si)22.4 (gnif)-32.5 (ic)-5.7 (ant r)9.6 (educ)-13.4 (t)-10.7 (ion )0.5 (in )0.5 (HC)19.9 (C b)20.4 (y im)20.9 (ple)]TJ
0 Tw 23.192 0 Td
(-)Tj
0.392 Tw -27.335 -1.426 Td
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[(ac)-13.3 (t)-10.7 (i)14.3 (v)23.9 (a)20 (t)13.6 (ed AP)-6.5 (C)-4.9 (s )0.5 (s)9 (t)-10.8 (imula)20.5 (t)13.6 (e )0.5 (T c)12.2 (e)30.4 (ll)3.8 (-medi)21.1 (a)19.9 (t)13.6 (ed immune )1.1 (r)9.6 (e)12.8 (s)15.4 (ponse )]TJ
0.53 Tw 0 -1.412 Td
[(a)20 (g)9.7 (ains)9.2 (t pr)8.5 (os)9.1 (t)-6.9 (a)20 (t)-10.8 (ic c)-5.8 (anc)12.1 (er c)12.2 (e)30.4 (lls)-4.4 (. S)30.9 (ipuleuc)12.4 (e)30.4 (l)3.6 (-)61.4 (T is )0.5 (the f)-32.8 (irs)9.1 (t )]TJ
0.013 Tw 0 -1.412 Td
[(FD)39.5 (A)3.7 (-)1.4 (appr)8.2 (o)25.5 (v)26.4 (ed )0.5 (ther)5.9 (apeut)-11 (ic )0.7 (c)-5.8 (anc)12.2 (er v)24 (ac)13.1 (cine )0.9 (used )0.5 (in )0.8 (me)16 (t)-6.9 (as)9 (t)-6.9 (a)19.9 (t)-10.8 (ic )]TJ
0 Tw 0 -1.412 Td
[(c)-5.9 (as)9 (t)-10.8 (r)5.7 (a)19.9 (t)13.7 (e)0.6 (-r)9.4 (e)12.9 (sis)9.3 (t)-6.9 (ant pr)8.5 (os)9.1 (t)-6.9 (a)19.9 (t)13.7 (e c)-5.8 (anc)12.2 (er \(mCR)-23.6 (P)-6.3 (C\).)]TJ
0.021 Tw 1.334 -1.412 Td
[(IMmuno)14.3 (t)0.5 (her)5.8 (ap)22.8 (y )0.6 (f)24.4 (or Pr)8.7 (os)9.1 (t)-6.9 (a)19.9 (t)13.7 (e )0.5 (A)17 (denoC)-10.2 (ar)13.5 (cinoma )0.9 (T)61 (r)9.6 (e)10.4 (a)19.9 (t)-10.8 (ment)-10.4 (, )]TJ
0.292 Tw -1.334 -1.412 Td
[(a P)16.1 (hase III t)-10.8 (r)-15.8 (i)21.2 (al)1.1 (, whic)15.9 (h r)5.7 (andomi)2.7 (z)8.3 (ed 512 mCR)-23.4 (P)-6.3 (C pa)19.8 (t)-10.8 (ient)-7 (s )]TJ
0.026 Tw 0 -1.412 Td
[(a)20 (t 2:1 t)15.6 (o r)9.6 (ec)12.3 (ei)14.5 (v)26.3 (e sipuleuc)12.6 (e)30.4 (l)3.6 (-)61.4 (T or plac)12.3 (e)22.1 (bo)7.3 (, adminis)9.4 (t)13.6 (er)9.7 (ed int)-10.6 (r)5.7 (a)]TJ
0 Tw (-)Tj
-0.04 Tw 0 -1.412 Td
[(v)26.4 (enousl)14.2 (y e)18.1 (v)26.4 (er)-31.8 (y 2 w)26.5 (ee)30.5 (k)-9.9 (s)-4.7 (, f)24.4 (or a t)15.6 (o)14.2 (t)-6.8 (al of t)0.5 (hr)9.6 (ee )0.5 (inf)-12 (usions)-4.2 (, demon)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.058 Tw -27.335 -1.412 Td
[(s)9 (t)-10.8 (r)5.7 (a)20 (t)13.6 (ed a medi)21.3 (an o)25.5 (v)26.4 (er)5.8 (all sur)-31.8 (v)-9.7 (i)14.4 (v)23.9 (al \(O)14.2 (S\) bene)23.2 (f)-32.7 (it of 4.1 mont)0.9 (hs )]TJ
0.069 Tw 0 -1.412 Td
[(\(25.8 )-0.7 (v)16.6 (s)-4.7 (. 21.7 )-0.6 (mont)0.8 (hs\) \()24.3 (ha)-4.4 (z)-4.4 (ar)11 (d )-0.6 (r)5.7 (a)20 (t)-10.8 (io [HR)20.4 (]: 0.751; )-0.8 (95% )-0.6 (c)13.6 (onf)-32.5 (i)]TJ
0 Tw 27.335 0 Td
(-)Tj
-0.014 Tw -27.335 -1.412 Td
[(denc)12.2 (e int)13.8 (er)-31.7 (v)23.9 (al [CI]: 0.606\2260.951; )]TJ
/TT2 1 Tf
0 Tw 15.247 0 Td
(p)Tj
/TT1 1 Tf
-0.014 Tw ( = 0.017\).)Tj
0 Tw 4.913 0 0 4.913 220.8691 532.3048 Tm
(19)Tj
-0.014 Tw 8.5 0 0 8.5 226.5594 529.3298 Tm
[( T)-17.7 (he mos)9.3 (t c)13.6 (om)]TJ
0 Tw 6.684 0 Td
(-)Tj
0.112 Tw -27.335 -1.412 Td
[(mon ad)12.9 (v)26.4 (erse e)18.2 (v)26.4 (ent)-7.2 (s as)11.4 (soci)21.4 (a)20 (t)13.6 (ed w)-7.7 (it)0.7 (h the sipuleuc)12.6 (e)30.4 (l)3.6 (-)61.4 (T g)-10.2 (r)8.6 (oup )]TJ
0.051 Tw 0 -1.412 Td
[(w)26.5 (er)9.7 (e inf)-12 (usional )0.5 (r)9.7 (e)10.3 (ac)-13.2 (t)-10.8 (ions )0.5 (suc)15.7 (h as c)15.7 (hills)-4.1 (, f)24.4 (e)18.2 (v)26.4 (er)53.7 (, and he)10.4 (ad)9.5 (ac)15.5 (he )]TJ
0.122 Tw 0 -1.412 Td
[(due t)15.6 (o r)9.6 (e)30.4 (le)10.5 (ase of c)-17.5 (yt)15.7 (ok)-12.8 (ine)13.1 (s)-4.7 (.)]TJ
0 Tw 4.913 0 0 4.913 160.4725 496.3048 Tm
(19)Tj
0.122 Tw 8.5 0 0 8.5 166.1627 493.3298 Tm
[( L)-28.4 (ac)15.6 (k of a)27.3 (v)23.9 (ailabilit)-27.2 (y)48 (, hi)22.2 (g)-1.4 (h c)13.7 (os)9 (t)-10.7 (, )]TJ
0.05 Tw -13.546 -1.412 Td
[(and )-0.7 (c)13.7 (om)20.8 (ple)11.9 (xit)-27.9 (y of pr)8.5 (oducin)14.7 (g sipuleuc)12.6 (e)30.3 (l)3.6 (-)61.4 (T cr)9.6 (e)10.4 (a)19.9 (t)13.6 (e an ob)11.7 (s)9 (t)-6.9 (ac)15.5 (le )]TJ
0 Tw 0 -1.412 Td
[(t)15.6 (o it)-7.1 (s r)8.8 (out)-10.7 (ine use)11.3 (.)]TJ
/TT0 1 Tf
0.02 Tc 9 0 0 9 51.0236 445.3298 Tm
[(DC)-20.6 (V)41.7 (a)-3.5 (x \(N)-1.3 (or)-26.3 (t)5 (hw)9.5 (e)6.5 (s)1.7 (t Bio)7.6 (t)5 (her)6.4 (apeut)4.5 (ic)-5 (s\))]TJ
/TT1 1 Tf
0 Tc 0.144 Tw 8.5 0 0 8.5 51.0236 433.3298 Tm
[(DC)-28.2 (V)57.6 (a)-22.1 (x is a f)16.1 (amil)13.8 (y of DC-based v)23.9 (ac)13.1 (cine )0.5 (c)13.6 (onsis)9.6 (t)-10.8 (in)14.9 (g of aut)15.4 (ol)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.099 Tw -27.335 -1.412 Td
[(o)9.9 (g)13.2 (ous DC)-4.9 (s r)9.6 (ec)13.8 (ombinant w)-7.6 (it)0.6 (h v)23.9 (ar)-15.9 (ious T)37 (A)-43.1 (A)-15.8 (s)-4.7 (. T)-17.6 (her)9.7 (e ar)9.5 (e thr)9.7 (ee )]TJ
0.061 Tw 0 -1.412 Td
[(separ)5.8 (a)20 (t)13.6 (e DC)-28.2 (V)57.6 (a)-22.1 (x pla)19.9 (tf)24.4 (or)-15.7 (ms)7.3 (: \(a\) DC)-28.1 (V)57.5 (a)-22 (x-Pr)8.3 (os)9.1 (t)-6.9 (a)20 (t)13.6 (e)10.9 (, \()16.5 (b\) DC)-28.2 (V)57.6 (a)-22 (x-L, )]TJ
0.126 Tw 0 -1.412 Td
[(and )-0.6 (\(c\) )-0.7 (DC)-28.4 (V)57.6 (a)-22.1 (x-Dir)9.8 (ec)-13 (t)-10.8 (. DC)-28.1 (V)57.5 (a)-22 (x-pr)8.1 (os)9 (t)-6.9 (a)19.9 (t)13.6 (e use)12.9 (s DC)-4.7 (s f)-12.2 (used w)-7.7 (it)0.6 (h )]TJ
0.482 Tw 0 -1.412 Td
[(r)9.6 (ec)13.8 (ombinant pr)8.5 (os)9.1 (t)-6.9 (a)19.9 (t)13.7 (e)0.6 (-)19.9 (s)15.3 (pecif)-32.6 (ic membr)6 (ane ant)-10.8 (i)22.1 (g)14.2 (en whole )]TJ
-0.022 Tw 0 -1.412 Td
[(pr)8.5 (o)14.3 (t)13.6 (ein, )0.9 (wher)9.9 (e)10.4 (as )0.5 (DC)-28.1 (V)57.5 (a)-22 (x-L w)26 (as )0.6 (de)17.9 (v)26.4 (e)30.4 (loped )0.5 (fr)8.6 (om )0.8 (dif)-14.2 (f)24.4 (er)9.8 (ent)-10.7 (i)21.2 (a)20 (t)13.6 (ed )]TJ
0 Tw 0 -1.412 Td
[(DC)-4.7 (s pulsed w)-7.5 (it)0.7 (h aut)15.5 (olo)10.1 (g)13.2 (ous whole t)-13.9 (umor l)13.9 (y)17.3 (s)2.1 (a)20 (t)13.6 (e)10.9 (.)]TJ
4.913 0 0 4.913 239.194 364.3048 Tm
(20)Tj
0.131 Tw 8.5 0 0 8.5 62.3622 349.3298 Tm
[(Pr)9.6 (e)18.2 (v)-9.7 (iousl)14.2 (y r)9.6 (epor)-23 (t)13.6 (ed P)16.2 (hase I/)-12.4 (II t)-10.8 (r)-15.7 (i)21.1 (als on DC)-28.2 (V)57.6 (a)-22 (x-L )-0.7 (sho)25.8 (w)26.4 (ed )]TJ
0.085 Tw -1.334 -1.412 Td
[(a sur)-31.9 (v)-9.8 (i)14.4 (v)23.9 (al bene)23.1 (f)-32.7 (it in ne)19.7 (w)15.3 (l)13.8 (y di)21 (a)19.9 (gnosed or r)9.6 (ec)-9.7 (ur)-15.8 (r)9.6 (ent g)-1.4 (lioblas)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.01 Tw -27.335 -1.412 Td
[(t)15.6 (oma )0.5 (mult)-10.6 (if)24.6 (or)-15.6 (me \(GBM\).)]TJ
0 Tw 4.913 0 0 4.913 147.6615 328.3048 Tm
(21)Tj
0.01 Tw 8.5 0 0 8.5 153.3517 325.3298 Tm
[( Sub)11.7 (seq)22.3 (uentl)13.9 (y)48 (, a P)16.2 (hase )0.5 (III t)-10.8 (r)-15.8 (i)21.2 (al w)26 (as )]TJ
0.09 Tw -12.039 -1.412 Td
[(init)-10.4 (i)21.2 (a)20 (t)13.6 (ed t)15.6 (o e)18.2 (v)23.9 (alua)19.9 (t)13.6 (e )0.5 (the )0.5 (addit)-11.1 (ion of )0.5 (DC)-28.2 (V)57.5 (a)-22 (x-L t)15.5 (o )0.5 (s)8.9 (t)-6.8 (and)9.5 (ar)11 (d of )]TJ
0.196 Tw 0 -1.412 Td
[(c)-5.9 (ar)9.6 (e f)24.4 (or ne)19.7 (w)15.2 (l)13.9 (y di)21.2 (a)19.9 (gnosed )0.6 (GBM. Af)-15.8 (t)13.6 (er sur)1.4 (g)14.2 (er)-31.8 (y )0.5 (and c)15.7 (hemo)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.256 Tw -27.335 -1.412 Td
[(r)5.7 (adio)14.2 (ther)5.9 (ap)22.7 (y)48 (, )0.5 (pa)19.8 (t)-10.8 (ient)-7 (s )0.5 (w)26.5 (er)9.7 (e )0.5 (r)5.7 (andomi)2.7 (z)8.3 (ed a)20 (t 2:1 t)15.5 (o )0.5 (r)9.6 (ec)12.3 (ei)14.5 (v)26.4 (e )]TJ
0.035 Tw 0 -1.412 Td
[(t)13.6 (emo)22.9 (z)9.3 (olomide )0.7 (plus DC)-28.2 (V)57.6 (a)-22.1 (x-L or t)13.7 (emo)22.9 (z)9.2 (olomide )0.8 (w)-7.7 (it)0.6 (h plac)12.2 (e)22.1 (bo)7.3 (, )]TJ
0.13 Tw 0 -1.412 Td
[(demons)9.3 (t)-10.8 (r)5.7 (a)19.9 (t)-10.7 (in)14.9 (g mode)12.7 (s)9 (t sur)-31.8 (v)-9.7 (i)14.3 (v)24 (al bene)23.2 (f)-32.7 (it w)-7.7 (it)0.6 (h f)24.4 (e)10.3 (asibilit)-27.1 (y and )]TJ
0 Tw 0 -1.412 Td
[(s)2.1 (af)24.4 (e)15.7 (t)-27.8 (y of t)0.7 (his appr)8.7 (oac)15.6 (h.)]TJ
4.913 0 0 4.913 141.195 256.3048 Tm
(22)Tj
/TT0 1 Tf
-0.035 Tc 0.035 Tw 9 0 0 9 51.0236 229.3298 Tm
[(G)-55.6 (VA)-89.5 (X)]TJ
/TT1 1 Tf
0 Tc 0.195 Tw 8.5 0 0 8.5 51.0236 217.3298 Tm
[(G)5.3 (V)78.5 (A)-40.2 (X )0.5 (v)24 (ac)13.2 (cine )0.8 (is )0.5 (the )0.7 (g)14.1 (ene)16 (t)-10.8 (ic )0.6 (modif)-32.8 (ic)-5.6 (a)19.9 (t)-10.8 (ion )0.9 (of )0.5 (whole )1.1 (t)-14.7 (umor )]TJ
0.099 Tw 0 -1.412 Td
[(c)12.2 (e)30.4 (lls t)15.5 (o secr)9.9 (e)15.7 (t)13.7 (e immune)0.9 (-)19.8 (s)9 (t)-10.7 (imula)20.4 (t)15.6 (or)-31.8 (y c)-17.6 (yt)15.7 (ok)-12.7 (ine)13 (s and )-0.7 (GM)3.3 (-)-23.1 (C)-9.8 (SF )]TJ
0.146 Tw 0 -1.412 Td
[(tha)20 (t le)10.6 (ads t)15.6 (o r)9.6 (ecr)-19.7 (uit)-10.6 (ment)-10.4 (, dif)-14.2 (f)24.4 (er)9.7 (ent)-10.7 (i)21.2 (a)19.9 (t)-10.8 (ion, )0.6 (and ac)-13.3 (t)-10.8 (i)14.4 (v)23.9 (a)20 (t)-10.8 (ion of )]TJ
0.006 Tw 0 -1.412 Td
[(DC)-4.7 (s )0.7 (a)19.9 (t )0.5 (in)31 (jec)-13.3 (t)-10.7 (ion )0.8 (sit)13.8 (e)12.8 (s)-4.7 (. )0.7 (T)-17.7 (he)12.9 (se )0.8 (ac)-13.3 (t)-10.8 (i)14.4 (v)23.9 (a)20 (t)13.6 (ed DC)-4.7 (s )0.7 (sub)11.7 (seq)22.3 (uentl)13.9 (y )0.7 (pr)8.4 (o)]TJ
0 Tw 27.335 0 Td
(-)Tj
-0.003 Tw -27.335 -1.412 Td
[(c)12.2 (e)12.8 (s)11.4 (s the t)-14.7 (umor ant)-10.8 (i)22.2 (g)14.1 (ens and pr)9.5 (e)12.8 (sent the)12.9 (se ant)-10.8 (i)22.2 (g)14.2 (ens t)15.6 (o T)61.5 (-c)12 (e)30.4 (lls )]TJ
0.025 Tw 0 -1.412 Td
[(w)-7.7 (it)0.6 (h t)-10.7 (r)5.7 (af)-14.3 (f)-32.7 (ic)15.8 (k)-12.8 (in)14.9 (g of T)61.4 (-c)12.1 (e)30.4 (lls int)15.8 (o dr)5.5 (ainin)15 (g l)13.8 (ym)20.9 (ph node)12.8 (s t)15.6 (o e)30.4 (licit )]TJ
0 Tw 0 -1.412 Td
[(ant)-10.8 (it)-14.5 (umor immune r)10.5 (e)12.8 (s)15.3 (ponse)11.1 (.)]TJ
4.913 0 0 4.913 164.902 148.3048 Tm
(23)Tj
0.417 Tw 8.5 0 0 8.5 62.3622 133.3298 Tm
[(W)-19 (hen G)5.3 (V)78.5 (A)-40.2 (X has been t)13.6 (e)12.8 (s)9 (t)13.7 (ed in hor)-15.7 (mone )0.5 (r)9.6 (e)23 (fr)5.7 (ac)-13.2 (t)15.6 (or)-31.8 (y )]TJ
0.448 Tw -1.334 -1.412 Td
[(pr)8.5 (os)9.1 (t)-6.9 (a)20 (t)13.6 (e c)-5.8 (anc)12.2 (er)53.6 (, hi)22.2 (g)-1.5 (h)-2.9 (-r)-15.9 (is)25.8 (k sur)1.4 (gic)-5.6 (all)13.9 (y r)9.6 (e)12.8 (sec)-12.8 (t)13.6 (ed me)30.7 (lanoma )]TJ
0.17 Tw 0 -1.412 Td
[(in )0.5 (ad)31.9 (ju)8.6 (v)23.9 (ant se)16 (t)-18.2 (t)-10.7 (in)14.8 (g)1.5 (s)-4.7 (, ad)13 (v)23.9 (anc)12.2 (ed pancr)9.4 (e)10.4 (a)19.9 (t)-10.7 (ic c)-5.8 (anc)12.2 (er and me)16 (t)]TJ
0 Tw (-)Tj
0.259 Tw 0 -1.412 Td
[(as)8.9 (t)-6.9 (a)20 (t)-10.8 (ic NS)7.5 (CL)-7.9 (C)-7.9 (, it sho)25.7 (w)26.5 (ed limit)14.4 (ed e)23.1 (f)-14.1 (f)-32.8 (ic)-5.6 (ac)-17.7 (y de)12.6 (s)15.4 (pit)13.6 (e s)9 (t)-10.8 (imu)]TJ
0 Tw (-)Tj
0.232 Tw 0 -1.412 Td
[(la)20.1 (t)-10.8 (in)14.9 (g immune )0.6 (r)9.6 (e)12.9 (s)15.3 (ponse)11 (.)]TJ
0 Tw 4.913 0 0 4.913 151.1145 88.3048 Tm
(24)Tj
(,)Tj
(25)Tj
(,)Tj
(26)Tj
(,)Tj
(27)Tj
0.232 Tw 8.5 0 0 8.5 177.3226 85.3298 Tm
[( T)78.5 (w)25.5 (o P)16.2 (hase III s)9 (t)-14.7 (udie)12.8 (s)-4.7 (, the )]TJ
0.279 Tw -14.859 -1.412 Td
[(V)-20.1 (I)-18.1 (T)37 (AL-1 and V)-20.1 (I)-18.1 (T)37 (AL-2 in )0.6 (me)16 (t)-6.9 (as)9 (t)-6.9 (a)19.9 (t)-10.8 (ic )0.6 (pr)8.5 (os)9.1 (t)-6.9 (a)20 (t)13.6 (e )0.5 (c)-5.8 (anc)12.1 (er)53.7 (, )0.5 (w)26.5 (er)9.7 (e )]TJ
0.095 Tw 0 -1.412 Td
[(t)13.6 (er)-15.6 (mina)20.4 (t)13.6 (ed e)10.4 (ar)11 (l)13.9 (y )0.5 (due t)15.5 (o )0.7 (lac)15.7 (k of )0.6 (t)0.5 (her)5.8 (apeut)-10.9 (ic )0.7 (e)23.1 (f)-14.2 (f)24.4 (ec)-13.1 (t)-10.8 (.)]TJ
0 Tw 4.913 0 0 4.913 249.0041 64.3048 Tm
(28)Tj
0.095 Tw 8.5 0 0 8.5 254.6943 61.3298 Tm
[( )0.5 (D)3.6 (e)12.8 (s)15.4 (pit)13.7 (e )]TJ
0.288 Tw -23.961 -1.412 Td
[(dis)2.1 (appoint)-10.8 (in)14.9 (g r)9.6 (e)12.8 (sult)-7 (s in pr)8.5 (os)9.1 (t)-6.9 (a)19.9 (t)13.7 (e c)-5.9 (anc)12.2 (er)53.7 (, one r)5.7 (andomi)2.7 (z)8.3 (ed )]TJ
-0.018 Tw 29.414 80.514 Td
[(P)16.1 (hase II t)-10.8 (r)-15.7 (i)21.1 (al in me)15.8 (t)-6.9 (as)8.9 (t)-6.9 (a)20 (t)-10.8 (ic pancr)9.5 (e)10.3 (a)20 (t)-10.8 (ic c)-5.9 (anc)12.2 (er)12.2 (; G)5.2 (V)78.6 (A)-40.2 (X im)20.9 (pr)8.5 (o)25.5 (v)26.4 (e)12.8 (s )]TJ
0 Tw 0 -1.412 Td
[(sur)-31.8 (v)-9.7 (i)14.3 (v)24 (al w)-7.6 (it)0.6 (h ac)13.2 (c)12.2 (ep)14.1 (t)-6.9 (able side e)23.5 (f)-14.1 (f)24.4 (ec)-13.1 (t)-7.4 (s)-4.7 (.)]TJ
4.913 0 0 4.913 443.6509 724.6774 Tm
(29)Tj
/TT0 1 Tf
0.02 Tc 9 0 0 9 301.0394 697.7024 Tm
[(R)21.1 (oc)-1.7 (apuldenc)11.6 (e)15.3 (l)-9.6 (-)49.5 (T \()11.2 (A)-12 (S)4.3 (G)-20.7 (-003\))]TJ
/TT1 1 Tf
0 Tc 0.338 Tw 8.5 0 0 8.5 301.0394 685.7024 Tm
[(R)21.8 (oc)-5.7 (apuldenc)12 (e)30.4 (l)3.6 (-)61.4 (T is a DC-based c)13.7 (o)-23.3 (-e)30.2 (lec)-12.9 (t)-10.8 (r)8.7 (opor)5.7 (a)20 (t)13.6 (ed v)23.9 (ac)13.1 (cine )]TJ
-0.064 Tw 0 -1.412 Td
[(de)18 (v)26.4 (e)30.3 (loped )0.5 (e)11.9 (x v)-9.7 (i)14.3 (v)25.4 (o )0.6 (fr)8.6 (om )0.8 (t)-26.4 (w)25.5 (o )0.6 (t)-27.9 (ype)12.8 (s )0.5 (of )0.5 (R)-23.6 (N)4.6 (A)-16.8 (, )0.6 (the )0.6 (pa)19.8 (t)-10.8 (ient\222)14.2 (s )0.6 (am)20.7 (pli)]TJ
0 Tw 27.335 0 Td
(-)Tj
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/TT1 1 Tf
0 Tc 0.104 Tw 8.5 0 0 8.5 65.1969 685.7024 Tm
[(Pr)8.7 (o)14.2 (t)13.7 (ein)-2.6 (-based pep)14 (t)-10.8 (ide )0.5 (v)23.9 (ac)13.1 (cine)13.1 (s )0.5 (ac)-13.1 (t v)-9.7 (i)21.2 (a the )0.5 (nor)-15.7 (mal )0.7 (pa)19.8 (t)0.5 (hw)26 (a)27.3 (y )]TJ
0.137 Tw 0 -1.412 Td
[(of ant)-10.8 (i)22.2 (g)14.1 (en up)14 (t)-6.9 (ak)30.1 (e)10.8 (, )0.5 (pr)8.4 (oc)12.3 (e)12.9 (s)11.4 (sin)15.1 (g)1 (, and pr)9.5 (e)12.8 (sent)-6.6 (a)20 (t)-10.8 (ion )0.7 (b)20.4 (y )0.5 (AP)-6.5 (C)-4.9 (s )0.5 (t)15.6 (o )]TJ
0.215 Tw 0 -1.412 Td
[(e)30.4 (licit )0.5 (immune r)9.6 (e)12.8 (s)15.3 (ponse a)20 (g)9.8 (ains)9.1 (t v)24 (ar)-15.9 (ious T)37 (A)-43.1 (A)-15.8 (s)-4.7 (. T)-17.7 (he)18.3 (y ar)9.5 (e of )]TJ
-0.031 Tw 0 -1.412 Td
[(thr)9.7 (ee )0.7 (t)-27.9 (ype)12.8 (s)7.1 (: sin)15.1 (g)-1.5 (le )0.8 (pep)14 (t)-10.8 (ide)10.9 (, )0.6 (mult)-10.5 (iple )0.6 (pep)14 (t)-10.8 (ide)10.9 (, )0.6 (and f)-12.2 (ull )0.7 (pr)8.5 (o)14.3 (t)13.6 (ein )]TJ
0 Tw 0 -1.412 Td
[(v)23.9 (ac)13.1 (cine)11.1 (.)]TJ
/TT0 1 Tf
0.02 Tc 9 0 0 9 65.1969 613.7024 Tm
[(N)-1.3 (e)15.3 (lipepimut-)49 (S \(G)8.2 (alena Biopharma\))]TJ
/TT1 1 Tf
0 Tc 0.428 Tw 8.5 0 0 8.5 65.1969 601.7024 Tm
[(N)12.9 (e)30.4 (lipepimut-)24.8 (S \(E75\) is )0.6 (a pep)14 (t)-10.8 (ide v)23.9 (ac)13.1 (cine )0.6 (der)-15.9 (i)14.3 (v)26.4 (ed fr)8.6 (om )]TJ
0.088 Tw 0 -1.412 Td
[(HER2 pr)8.5 (o)14.3 (t)13.6 (ein pr)9.5 (e)12.8 (sent in br)9.5 (e)10.4 (as)8.9 (t c)-5.8 (anc)12.1 (er c)12.2 (e)30.4 (lls )0.6 (t)15.6 (o pr)8.4 (oduc)12.1 (e s)15.4 (pe)]TJ
0 Tw (-)Tj
0.199 Tw 0 -1.412 Td
[(cif)-32.5 (ic )0.7 (imm)0.6 (une )0.6 (r)9.6 (e)12.8 (s)15.4 (ponse)13 (s)-4.7 (. )0.6 (Based )0.5 (on )0.6 (a P)16.1 (hase )0.8 (I/)-12.3 (II t)-10.7 (r)-15.8 (i)21.2 (al )0.6 (wher)9.8 (e )]TJ
0.146 Tw 0 -1.412 Td
[(pa)19.8 (t)-10.8 (ient)-7 (s w)-7.7 (it)0.7 (h hi)22.2 (g)-1.4 (h)-2.9 (-r)-15.9 (is)25.8 (k br)9.5 (e)10.4 (as)8.9 (t c)-5.9 (anc)12.2 (er r)9.6 (ec)12.3 (ei)14.5 (v)-9.7 (in)14.8 (g the v)23.9 (ac)13.1 (cine )]TJ
0.211 Tw 0 -1.412 Td
[(had im)21 (pr)8.5 (o)25.5 (v)26.3 (ed dise)10.6 (ase)0.7 (-)6.2 (fr)9.6 (ee sur)-31.7 (v)-9.8 (i)14.4 (v)23.9 (al)1.1 (, a P)16.1 (hase III \(P)15 (R)-23.6 (E)-7.8 (SEN)-21.6 (T)15 (\) )]TJ
0.528 Tw 0 -1.412 Td
[(s)9 (t)-14.7 (ud)12.9 (y )0.5 (s)9 (t)-6.9 (ar)-23.1 (t)13.6 (ed in 2014 c)13.6 (om)20.9 (par)9.6 (ed ne)30.4 (lipepimut-)24.8 (S )0.6 (v)26.3 (ersus )]TJ
-0.014 Tw 0 -1.412 Td
[(GM)3.2 (-)-23.1 (C)-9.8 (SF in pa)19.8 (t)-10.7 (ient)-7.1 (s w)-7.6 (it)0.6 (h node)0.5 (-posit)-10.6 (i)14.4 (v)26.4 (e HER2 lo)25.6 (w)13.3 (-e)11.7 (xpr)9.3 (e)12.9 (s)11.4 (sin)15.1 (g )]TJ
0.115 Tw 0 -1.412 Td
[(br)9.5 (e)10.4 (as)8.9 (t c)-5.9 (anc)12.2 (er)53.7 (. T)-17.7 (his )0.7 (t)-10.8 (r)-15.8 (i)21.2 (al w)26 (as s)8.9 (t)15.6 (opped due t)15.5 (o f)-12.2 (ut)-10.9 (ilit)-27.3 (y in )0.5 (June )]TJ
0 Tw 0 -1.412 Td
[(2016 af)-16.2 (t)13.7 (er an int)13.8 (er)-15.7 (im r)10.1 (e)18.2 (v)-9.8 (ie)19.8 (w)45.1 (.)]TJ
4.913 0 0 4.913 178.7474 508.6774 Tm
(37)Tj
(,)Tj
(38)Tj
/TT0 1 Tf
0.02 Tc 9 0 0 9 65.1969 481.7024 Tm
[(Gly)15.3 (c)13.5 (opr)-1 (o)7.7 (t)10.3 (ein 100)]TJ
/TT1 1 Tf
0 Tc 0.691 Tw 8.5 0 0 8.5 65.1969 469.7024 Tm
[(T)-17.7 (his )0.7 (v)23.9 (ac)13.2 (cine )0.6 (w)26 (as de)18 (v)26.4 (e)30.4 (loped usin)15 (g me)30.6 (lanoma-)19.9 (s)15.3 (pecif)-32.5 (ic )]TJ
0.159 Tw 0 -1.412 Td
[(immuno)10.5 (g)14.2 (enic pep)14 (t)-10.7 (ide of g)-1.5 (l)13.8 (y)25.6 (c)13.7 (opr)8.5 (o)14.3 (t)13.6 (ein 100 )-0.6 (\(Gp100\) )-1.1 (\(amino )]TJ
0.204 Tw 0 -1.412 Td
[(acids 209\226217\) )-1 (in c)13.7 (ombina)20.4 (t)-10.8 (ion w)-7.7 (it)0.7 (h an immune)1.3 (-)1.3 (ad)32 (ju)8.5 (v)24 (ant )]TJ
0.315 Tw 0 -1.412 Td
[(Mont)-6.8 (anide IS)16.2 (A)3.8 (-51. A P)16.2 (hase II t)-10.8 (r)-15.8 (i)21.2 (al w)26 (as c)13.7 (onduc)-13.4 (t)13.7 (ed usin)15 (g )]TJ
0.182 Tw 0 -1.412 Td
[(Gp100 w)-7.7 (it)0.7 (h int)13.9 (er)11.1 (leuk)-12.6 (in )0.6 (\(IL)66.2 (\)-2 c)13.6 (ombina)20.4 (t)-10.8 (ion, )0.8 (whic)15.9 (h sho)25.8 (w)26.5 (ed )]TJ
0.27 Tw 0 -1.412 Td
[(an im)21 (pr)8.5 (o)25.5 (v)26.3 (ed ob)24.9 (jec)-13.2 (t)-10.8 (i)14.4 (v)26.3 (e )0.6 (r)9.6 (e)12.8 (s)15.4 (ponse )0.5 (r)5.7 (a)19.9 (t)13.7 (e )0.5 (c)13.7 (om)20.8 (par)9.4 (ed w)-7.7 (it)0.7 (h )0.5 (tha)20 (t )]TJ
0.177 Tw 0 -1.412 Td
[(of t)0.5 (he )0.5 (pr)9.6 (e)18.2 (v)-9.8 (ious )0.8 (r)9.6 (e)12.8 (sult )0.6 (of IL-2 alone)11.2 (.)]TJ
0 Tw 4.913 0 0 4.913 209.7592 400.6774 Tm
(39)Tj
0.177 Tw 8.5 0 0 8.5 215.4494 397.7024 Tm
[( A P)16.1 (hase )0.7 (III t)-10.8 (r)-15.8 (i)21.2 (al )0.5 (w)26 (as )]TJ
0.076 Tw -17.677 -1.412 Td
[(or)1.4 (g)9.8 (ani)2.6 (z)8.3 (ed t)0.5 (ha)20 (t r)5.7 (andomi)2.8 (z)8.3 (ed 177 pa)20 (t)-10.8 (ient)-7 (s of S)27.4 (t)-6.9 (a)20 (g)14.2 (e III/)-12.4 (I)-18.1 (V me)30.6 (l)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.207 Tw -27.335 -1.412 Td
[(anoma )0.8 (t)15.5 (o )0.7 (IL-2 alone )0.9 (or )0.5 (c)13.7 (ombina)20 (t)-10.8 (ion )0.8 (r)9.7 (e)7.4 (gimen. )1.3 (A)16.9 (ddit)-11 (ion )0.8 (of )]TJ
0.179 Tw 0 -1.412 Td
[(v)23.9 (ac)13.1 (cine sho)25.7 (w)26.5 (ed a hi)22.2 (g)-1.5 (her c)15.6 (linic)-5.2 (al r)9.6 (e)12.8 (s)15.3 (ponse r)5.7 (a)19.9 (t)13.7 (e \(16 v)16.6 (s)-4.7 (. 6%; )]TJ
0 Tw 27.746 0 Td
( )Tj
/TT3 1 Tf
-27.746 -1.412 Td
(p)Tj
/TT1 1 Tf
0.371 Tw [( = 0.03\) and pr)8.5 (olon)15.1 (g)14.1 (ed pr)8.5 (o)9.8 (g)-10.2 (r)9.6 (e)12.8 (s)11.4 (sion)-2.3 (-)6.2 (fr)9.6 (ee )0.5 (sur)-31.8 (v)-9.8 (i)14.4 (v)23.9 (al \(P)15 (F)-8.5 (S\) )]TJ
0 Tw 0 -1.412 Td
[(\(2.2 v)16.4 (s)-4.7 (. 1.6 mont)1 (hs)4.1 (; )]TJ
/TT3 1 Tf
(p)Tj
/TT1 1 Tf
( = 0.008\).)Tj
4.913 0 0 4.913 184.1927 340.6774 Tm
(40)Tj
/TT0 1 Tf
0.02 Tc 9 0 0 9 65.1969 313.7024 Tm
[(T)68.8 (ec)11.5 (emo)7.6 (t)4.5 (ide \(C)-4.5 (a)11.1 (sc)-1.7 (adi)7.9 (an Ther)6.4 (apeut)4.4 (ic)-5.1 (s\))]TJ
/TT1 1 Tf
0 Tc 0.365 Tw 8.5 0 0 8.5 65.1969 301.7024 Tm
[(T)76.6 (ec)12.3 (emo)14.6 (t)-10.8 (ide \(L-BLP25\) is )0.5 (a mucin )0.5 (1 \(MUC1 g)-1.4 (l)13.8 (y)25.5 (c)13.7 (opr)8.6 (o)14.3 (t)13.6 (ein )]TJ
0.641 Tw 0 -1.412 Td
[(e)11.8 (xpr)9.3 (e)12.9 (s)11.4 (sed in NS)7.6 (CL)-7.9 (C\) ant)-10.8 (i)22.2 (g)14.1 (en)-2.7 (-)19.9 (s)15.3 (pecif)-32.6 (ic pep)14 (t)-10.8 (ide v)23.9 (ac)13.1 (cine)11.1 (, )]TJ
0.763 Tw 0 -1.412 Td
[(c)-5.9 (apable of )0.5 (inducin)14.9 (g c)12.3 (e)30.3 (ll)3.8 (-medi)21.2 (a)20 (t)13.6 (ed immune )1.1 (r)9.6 (e)12.9 (s)15.3 (ponse )]TJ
0.082 Tw 0 -1.412 Td
[(a)20 (g)9.7 (ains)9.2 (t MUC1 )0.5 (pr)8.5 (o)14.3 (t)13.6 (ein )0.8 (t)0.5 (ha)20 (t w)26 (as )0.7 (t)13.6 (e)12.8 (s)9 (t)13.6 (ed in )0.8 (pr)9.5 (ec)15.7 (linic)-5.3 (al )0.7 (s)8.9 (t)-14.6 (udie)12.7 (s)-4.7 (. )]TJ
0 Tw 27.746 0 Td
( )Tj
0.285 Tw -27.746 -1.412 Td
[(Af)-15.8 (t)13.6 (er pr)8.5 (omisin)15.7 (g r)9.6 (e)12.9 (sult)-7.1 (s in a P)16.2 (hase II t)-10.8 (r)-15.8 (i)21.2 (al)1.1 (, a r)5.7 (andomi)2.8 (z)8.2 (ed )]TJ
0 Tw 27.746 0 Td
( )Tj
0.247 Tw -27.746 -1.412 Td
[(P)16.1 (hase )0.5 (III t)-10.8 (r)-15.8 (i)21.2 (al \(S)-8.8 (T)37 (AR)-5.2 (T)15 (\) w)26 (as init)-10.3 (i)21.1 (a)20 (t)13.6 (ed amon)15 (g pa)19.8 (t)-10.7 (ient)-7.1 (s w)-7.7 (it)0.6 (h )]TJ
0.38 Tw 0 -1.412 Td
[(unr)9.6 (e)12.8 (sec)-12.9 (t)-6.9 (able )0.5 (S)27.4 (t)-6.8 (a)19.9 (g)14.2 (e III NS)7.6 (CL)-7.9 (C)-7.8 (, af)-15.7 (t)13.6 (er c)15.6 (hemor)6.2 (adi)20.9 (a)20 (t)-10.8 (ion )0.7 (as a )]TJ
-0.015 Tw 0 -1.412 Td
[(maint)14 (enanc)12.4 (e ther)5.7 (ap)22.8 (y w)-7.7 (it)0.6 (h this )0.5 (v)23.9 (ac)13.2 (cine)11.1 (.)]TJ
0 Tw 4.913 0 0 4.913 217.8071 220.6774 Tm
(41)Tj
-0.015 Tw 8.5 0 0 8.5 223.4973 217.7024 Tm
[( T)-17.7 (he medi)21.3 (an O)14.4 (S w)26 (as )]TJ
-0.032 Tw -18.624 -1.412 Td
[(similar be)15.6 (t)-26.4 (w)26.5 (een bo)14.2 (th g)-10.3 (r)8.7 (oups \(25.6 )-0.7 (v)16.6 (s)-4.7 (. 22.3 mont)0.8 (hs)-4.6 (, HR: )-0.7 (0.88; )]TJ
0 Tw 27.746 0 Td
( )Tj
/TT3 1 Tf
-27.746 -1.412 Td
(p)Tj
/TT1 1 Tf
0.284 Tw [( = 0.123\), but v)24 (ac)13.1 (cina)20.2 (t)13.6 (ed pa)19.8 (t)-10.8 (ient)-7.2 (s sho)25.7 (w)26.5 (ed an im)20.9 (pr)8.5 (o)25.5 (v)26.4 (ed )]TJ
0.132 Tw 0 -1.412 Td
[(sec)14 (ond)9.7 (ar)-32 (y end point of t)-10.8 (ime)1.1 (-)1.3 (t)15.6 (o)-23.3 (-)19.8 (sym)20.8 (p)14.1 (t)15.6 (om )0.5 (pr)8.5 (o)9.9 (g)-10.3 (r)9.7 (e)12.8 (s)11.4 (sion )0.8 (\(HR: )]TJ
0 Tw 0 -1.412 Td
(0.85; )Tj
/TT3 1 Tf
2.689 0 Td
(p)Tj
/TT1 1 Tf
0.117 Tw [( )0.5 (= )0.7 (0.023\). )0.5 (A sub)6.4 (g)-10.3 (r)8.6 (oup )0.5 (anal)13.7 (y)17.2 (sis )1.2 (r)9.6 (e)18.1 (v)26.4 (e)10.4 (aled )0.5 (a )0.5 (si)22.3 (gnif)-32.4 (ic)-5.7 (ant )]TJ
0.34 Tw -2.689 -1.412 Td
[(im)21 (pr)8.4 (o)25.5 (v)26.4 (ement of medi)21.3 (an O)14.3 (S of t)0.5 (hose who r)9.6 (ec)12.3 (ei)14.5 (v)26.4 (ed pr)9.5 (e)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.366 Tw -27.335 -1.412 Td
[(v)-9.8 (ious c)13.6 (onc)-9.6 (ur)-15.9 (r)9.7 (ent c)15.6 (hemor)6.2 (adi)20.9 (a)20 (t)-10.8 (ion \(30.8 )-0.6 (v)16.6 (s)-4.7 (. 20.6 mont)0.8 (hs)-4.6 (, )]TJ
0 Tw 27.746 0 Td
( )Tj
/TT3 1 Tf
-27.746 -1.412 Td
(p)Tj
/TT1 1 Tf
( = 0.016\).)Tj
4.913 0 0 4.913 105.6757 136.6774 Tm
(41)Tj
/TT0 1 Tf
0.02 Tc 9 0 0 9 65.1969 109.7024 Tm
[(Rindopepimut \(Rint)10.3 (eg)6.2 (a\))]TJ
/TT1 1 Tf
0.007 Tc 0.087 Tw 8.5 0 0 8.5 65.1969 97.7024 Tm
[(Epider)-15.8 (mal )0.5 (g)-10.2 (r)8.7 (o)25.4 (w)-19.4 (t)0.5 (h )0.6 (f)16.1 (ac)-13.2 (t)15.6 (or )0.6 (r)9.6 (ec)12.2 (ep)14.1 (t)15.5 (or )0.6 (v)23.9 (ar)-15.8 (i)21.2 (ant )0.5 (III )0.5 (\(EGFRvIII\) )0.6 (is )0.6 (a)6.9 ( )]TJ
0.15 Tw 0 -1.412 Td
[(t)-27.9 (ype of de)30.4 (le)15.7 (t)-10.8 (ion mut)-6.9 (a)20 (t)-10.8 (ion of EGFR of)-15.6 (t)13.6 (en o)25.5 (v)26.4 (er)9.6 (e)11.9 (xpr)9.7 (e)12.8 (s)11.4 (sed in)7.1 ( )]TJ
0.12 Tw 0 -1.412 Td
[(pr)-15.8 (imar)-31.9 (y GBM pa)19.9 (t)-10.7 (ient)-7.4 (s)-4.6 (. Rindopepimut \(C)-5.4 (D)50.5 (X)47.9 (-110\) is a pep)]TJ
0 Tc 0 Tw 27.335 0 Td
(-)Tj
0.007 Tc 0.152 Tw -27.335 -1.412 Td
[(t)-10.8 (ide v)23.9 (ac)13.2 (cine t)0.5 (ha)20 (t s)15.3 (pans t)0.5 (he len)14.7 (g)-17.5 (th of EGFRvIII, c)13.7 (on)30.8 (ju)20.9 (g)9.8 (a)19.9 (t)13.7 (ed)6.8 ( )]TJ
0.046 Tw 29.414 79.059 Td
[(w)-7.7 (ith c)-5.8 (ar)-15.7 (r)-15.8 (ier pr)8.6 (o)14.3 (t)13.6 (ein k)30.2 (e)18.2 (yhole lim)20.8 (pe)15.8 (t hemoc)-17.6 (y)24.6 (anin. A P)16.1 (hase II)7 ( )]TJ
-0.059 Tw 0 -1.412 Td
[(t)-10.8 (r)-15.8 (i)21.2 (al \()61.9 (A)30.1 (C)-28.4 (T III\) w)-7.7 (it)0.5 (h ne)19.7 (w)15.2 (l)13.9 (y di)21.2 (a)19.9 (gnosed GBM sho)25.5 (w)26.5 (ed an incr)9.7 (e)10.3 (ase)7.1 ( )]TJ
0.236 Tw 0 -1.412 Td
[(in P)15.1 (F)-8.5 (S and O)14.4 (S amon)14.7 (g v)23.9 (ac)13.1 (cina)19.9 (t)13.7 (ed pa)19.9 (t)-10.8 (ient)-7.3 (s o)25.5 (v)26.4 (er his)9 (t)15.6 (or)-15.8 (ic)-5.8 (al)7.2 ( )]TJ
0.06 Tw 0 -1.412 Td
[(c)13.7 (ont)-10.8 (r)8.7 (ol)1.1 (, )0.6 (but )0.5 (a )0.6 (sub)11.6 (seq)22 (uent )0.5 (P)16.1 (hase )0.5 (III )0.6 (t)-10.8 (r)-15.8 (i)21.2 (al )0.5 (f)24.4 (ound )0.5 (disc)13.7 (our)5.7 (a)20 (gin)14.7 (g)7 ( )]TJ
-0.007 Tw 0 -1.412 Td
[(r)9.6 (e)12.8 (sult)-10.8 (.)]TJ
4.913 0 0 4.913 340.0915 688.6774 Tm
(42)Tj
0 Tc 0 Tw (,)Tj
0.007 Tc -0.007 Tw 1.413 0 Td
(43)Tj
/TT0 1 Tf
0.02 Tc 0 Tw 9 0 0 9 315.2126 661.7024 Tm
[(Be)15.3 (lagen)0.8 (puma)7.2 (t)3 (uc)11.5 (e)15.3 (l)-9.6 (-L \(L)4.9 (uc)-1.6 (anix\))]TJ
/TT1 1 Tf
0 Tc 0.454 Tw 8.5 0 0 8.5 315.2126 649.7024 Tm
[(Be)30.4 (la)20.1 (g)14.2 (en)20.2 (puma)19.9 (t)-14.7 (uc)12.2 (e)30.4 (l)3.6 (-L is a v)23.9 (ac)13.1 (cine pr)8.4 (oduc)12.1 (ed fr)8.7 (om ir)-15.6 (r)5.7 (adi)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.227 Tw -27.335 -1.412 Td
[(a)20 (t)13.6 (ed allo)10.1 (g)14.2 (eneic )0.6 (NS)7.6 (CL)-7.9 (C c)12.2 (e)30.4 (lls )0.6 (t)-10.8 (r)5.7 (ans)16.3 (f)24.4 (ec)-13 (t)13.6 (ed w)-7.7 (it)0.6 (h t)-10.8 (r)5.7 (ans)16.3 (f)24.4 (or)-15.7 (min)15.1 (g )]TJ
/C2_0 1 Tf
0 Tw 0 -1.412 Td
[<004A>-10.2 <0055>8.6 <0052>25.5 <005A>-19.4 <0057004B0003>-190.1 <0049>16.1 <00440046>-13.2 <0057>15.6 <005200550003>-190.2 <01F5001000150003>-190.2 <004400510057>-10.8 <004C005600480051005600480003>-189.3 <004A>14.2 <0048005100480003>-189.9 <0053004F004400560050004C0047>-0.6 <00110003>-190 <002C00510003>-190.1 <00440003>-190.2 <00470052005600480003>-189.9 <0059>23.9 <00440055>-15.8 <004C>]TJ
/TT1 1 Tf
27.335 0 Td
(-)Tj
0.233 Tw -27.335 -1.412 Td
[(able)10.9 (, r)5.7 (andomi)2.7 (z)8.3 (ed P)16.1 (hase II t)-10.8 (r)-15.7 (i)21.1 (al)1.1 (, 75 pa)19.8 (t)-10.8 (ient)-7 (s w)-7.7 (it)0.6 (h S)27.5 (t)-6.9 (a)19.9 (g)14.2 (e II, )]TJ
0.046 Tw 0 -1.412 Td
[(III)-18.2 (A)-16.8 (, IIIB, and I)-18.2 (V \()61.9 (A)13 (JC)19.9 (C 6)]TJ
0 Tw 4.913 0 0 4.913 407.4216 604.6774 Tm
[(t)0.5 (h)]TJ
0.046 Tw 8.5 0 0 8.5 412.229 601.7024 Tm
[( edit)-10.7 (ion\) NS)7.7 (CL)-7.9 (C r)9.7 (ec)12.3 (ei)14.5 (v)26.3 (ed one of t)0.5 (he )]TJ
0.112 Tw -11.414 -1.412 Td
[(thr)9.7 (ee )0.5 (dose)13 (s )0.5 (of v)24 (ac)13.1 (cine )0.6 (\(1.25, 2.5, or 5 \327 )0.5 (10)]TJ
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(7)Tj
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[( c)12.2 (e)30.4 (lls/)-1.9 (in)31 (jec)-13.3 (t)-10.8 (ion\). )]TJ
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( )Tj
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(7)Tj
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[( c)12.2 (e)30.4 (lls )0.9 (per in)31 (jec)-13.3 (t)-10.7 (ion )]TJ
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(\()Tj
/TT3 1 Tf
(p)Tj
/TT1 1 Tf
-0.003 Tw ( = 0.0069\).)Tj
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(44)Tj
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[( L)-28.3 (a)19.9 (t)13.6 (er on, a phase III r)5.7 (andomi)2.8 (z)8.2 (ed t)-10.7 (r)-15.8 (i)21.2 (al w)26 (as c)13.7 (on)]TJ
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(-)Tj
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[(duc)-13.5 (t)13.7 (ed w)-7.7 (it)0.7 (h s)9 (t)-6.8 (a)19.9 (g)14.2 (e III-I)-18.5 (V NS)7.7 (CL)-7.9 (C pa)19.8 (t)-10.8 (ient)-7 (s who did no)14.3 (t pr)8.5 (o)9.9 (g)-10.3 (r)9.6 (e)12.9 (s)11.4 (s )]TJ
0.045 Tw 0 -1.412 Td
[(af)-15.7 (t)13.6 (er pla)20 (t)-10.8 (inum )0.7 (based c)15.7 (hemo)14.6 (t)0.5 (her)5.8 (ap)22.8 (y)48 (, t)15.6 (o r)9.6 (ec)12.3 (ei)14.5 (v)26.4 (e maint)14 (enanc)12.4 (e )]TJ
0.263 Tw 0 -1.412 Td
[(Be)30.4 (la)20.1 (g)14.2 (en)20.2 (puma)19.9 (t)-14.7 (uc)12.2 (e)30.4 (l)3.6 (-L or plac)12.1 (e)22.1 (bo)7.4 (. T)-17.7 (he medi)21.3 (an sur)-31.8 (v)-9.7 (i)14.3 (v)24 (al w)26 (as )]TJ
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[(similar )1.2 (amon)15 (g )0.5 (the )0.6 (o)25.5 (v)26.3 (er)5.9 (all )0.6 (c)13.7 (ohor)-22.8 (t \(20.3 mont)0.8 (hs )0.7 (f)24.4 (or v)23.9 (ac)13.2 (cine )]TJ
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[(g)-10.2 (r)8.6 (oup v)16.6 (s)-4.7 (. 17.8 mont)0.9 (hs f)24.4 (or plac)12.2 (e)22.1 (bo)7.4 (, )]TJ
/TT3 1 Tf
0 Tw (p)Tj
/TT1 1 Tf
0.062 Tw [( = 0.594\), but sub)6.4 (g)-10.2 (r)8.6 (oup )]TJ
0.153 Tw 0 -1.412 Td
[(anal)13.8 (y)17.2 (sis )0.6 (r)9.6 (e)18.2 (v)26.4 (e)10.3 (aled tha)20 (t pa)19.8 (t)-10.8 (ient)-7 (s r)9.6 (ec)12.3 (ei)14.5 (v)-9.7 (in)14.8 (g v)23.9 (ac)13.1 (cine w)-7.7 (it)0.6 (hin 12 )]TJ
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[(w)26.5 (ee)30.5 (k)-9.9 (s )0.5 (of c)13.7 (om)20.8 (ple)15.8 (t)-10.8 (ion )0.7 (of c)15.7 (hemo)14.6 (t)0.5 (her)5.8 (ap)22.8 (y )0.5 (had a lon)15 (g)14.1 (er medi)21.3 (an )]TJ
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[(sur)-31.8 (v)-9.7 (i)14.3 (v)24 (al \(20.7 v)16.3 (s)-4.6 (. 13.3 mont)0.8 (hs)-4.7 (, )]TJ
/TT3 1 Tf
(p)Tj
/TT1 1 Tf
( = 0.092\).)Tj
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(45)Tj
(,)Tj
(46)Tj
/TT2 1 Tf
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[(DN)1.3 (A and R)-1.1 (N)1.4 (A V)42 (ac)10.1 (cine)5.8 (s)]TJ
/TT1 1 Tf
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0.291 Tw 0 -1.412 Td
[(in v)23.9 (ac)13.1 (cine t)13.6 (ec)15.7 (hnolo)10.2 (g)-27.9 (y usin)15.1 (g DN)4.8 (A \(as a plasmid)49.2 (\) or R)-23.6 (N)4.6 (A )]TJ
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( )Tj
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[(\(as mR)-23.6 (N)4.6 (A)59.8 (\) t)0.5 (ha)20 (t is )0.7 (t)-6.9 (ak)30 (en up b)20.4 (y AP)-6.5 (C)-4.9 (s and t)-10.8 (r)5.7 (ansla)20.3 (t)13.6 (ed int)15.8 (o )]TJ
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0.067 Tw 0 -1.412 Td
[(immunit)-27 (y)48 (. T)60.9 (r)5.7 (ans)16.3 (f)24.4 (ec)-13.1 (t)13.7 (ed c)12.2 (e)30.4 (lls )0.7 (e)11.9 (xpr)9.2 (e)12.9 (s)11.4 (s the ant)-10.8 (i)22.2 (g)14.2 (en enc)13.8 (oded on )]TJ
0.141 Tw 0 -1.412 Td
[(plasmid )0.6 (DN)4.8 (A t)15.6 (o AP)-6.5 (C)-4.9 (s)-4.7 (, e)23 (f)-14.1 (f)24.4 (ec)-13.1 (t)-10.8 (i)14.4 (v)26.4 (e)30.4 (l)13.8 (y en)14.8 (g)9.8 (a)20 (gin)14.9 (g bo)14.1 (t)0.5 (h ma)30.4 (jor his)]TJ
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(-)Tj
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[(t)15.6 (oc)13.7 (om)20.9 (pa)19.8 (t)-10.8 (ibilit)-27.2 (y c)13.6 (om)20.9 (ple)11.9 (x \(MHC-I\))-0.7 ( and MHC-II )-0.7 (pa)19.8 (t)0.5 (hw)26 (a)27.3 (y)17.2 (s w)-7.7 (it)0.7 (h )]TJ
-0.029 Tw 0 -1.412 Td
[(r)9.6 (ecr)-19.6 (uit)-10.6 (ment of C)-5.5 (D8)]TJ
0 Tw 4.913 0 0 4.913 389.985 340.6774 Tm
(+)Tj
-0.029 Tw 8.5 0 0 8.5 392.6813 337.7024 Tm
[( and C)-5.4 (D4)]TJ
0 Tw 4.913 0 0 4.913 427.2323 340.6774 Tm
(+)Tj
-0.029 Tw 8.5 0 0 8.5 429.9286 337.7024 Tm
[( T)61.4 (-c)12.1 (e)30.3 (lls)-4.3 (, r)9.6 (e)12.8 (sult)-10.5 (in)14.9 (g in an immune )]TJ
0 Tw -13.496 -1.412 Td
[(r)9.6 (e)12.8 (s)15.4 (ponse)11 (.)]TJ
4.913 0 0 4.913 351.8564 328.6774 Tm
(47)Tj
0.026 Tc 0.27 Tw 8.5 0 0 8.5 326.5512 313.7024 Tm
[(T)-17.7 (her)9.6 (e ar)9.6 (e dif)-14.2 (f)24.4 (er)9.6 (ent k)-12.8 (inds of g)14.1 (ene)15.7 (t)-10.8 (ic v)23.9 (ac)13.2 (cine)12.8 (s t)13.6 (e)12.8 (s)9 (t)13.7 (ed)25.7 ( )]TJ
0.133 Tw -1.334 -1.412 Td
[(in )0.6 (se)18.2 (v)26.3 (er)5.7 (al )0.5 (c)15.6 (linic)-5.8 (al )0.5 (t)-10.8 (r)-15.8 (i)21.2 (als )0.5 (suc)15.6 (h )0.5 (as )0.5 (P)59.1 (AP )0.5 (f)24.4 (or )0.5 (pr)8.6 (os)9 (t)-6.9 (a)20 (t)13.6 (e )0.5 (c)-5.8 (anc)12.3 (er)53.5 (,)26.1 ( )]TJ
0.189 Tw 0 -1.412 Td
[(mamma)19.9 (g)-1.4 (lobin)-2.8 (-)9.1 (A DN)4.6 (A v)24 (ac)13.2 (cine f)24.4 (or br)9.6 (e)10.4 (as)8.9 (t c)-5.8 (anc)12.2 (er)53.5 (, human)26 ( )]TJ
-0.015 Tw 0 -1.412 Td
[(t)-27.9 (yr)8.6 (osinase)0.6 (-r)9.6 (e)30.4 (la)20 (t)13.6 (ed pr)8.7 (o)14.2 (t)13.7 (ein 1 also c)-5.9 (alled g)-11.3 (p75 g)-1.4 (l)13.8 (y)25.6 (c)13.6 (opr)8.6 (o)14.3 (t)13.6 (ein)26.1 ( )]TJ
-0.077 Tw 0 -1.412 Td
[(\()15 (T)77.1 (yr)-16.8 (p1/)-3.4 (g)-11.3 (p75\) f)24.4 (or me)30.3 (lanoma)-5.4 (, and VXM01, an or)5.7 (al T c)12.2 (e)30.4 (ll v)23.9 (ac)]TJ
0 Tc 0 Tw (-)Tj
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[(cine )0.5 (a)19.9 (g)9.8 (ains)9 (t )0.5 (v)24 (asc)-9.8 (ular )0.5 (endo)14.3 (t)0.5 (he)30.4 (li)21.2 (al )0.5 (g)-10.3 (r)8.7 (o)25.4 (w)-19.4 (t)0.5 (h )0.5 (f)16.1 (ac)-13.2 (t)15.6 (or )0.5 (r)9.6 (ec)12.2 (ep)14 (t)15.6 (or)25.8 ( )]TJ
0.109 Tw 0 -1.412 Td
[(2 f)24.4 (or ad)13 (v)24 (anc)12.2 (ed pancr)9.6 (e)10.4 (a)19.9 (t)-10.8 (ic c)-5.9 (anc)12.2 (er)53.6 (.)]TJ
-0.026 Tw 4.913 0 0 4.913 455.1176 244.6774 Tm
(48)Tj
0 Tc 0 Tw (-)Tj
0.026 Tc -0.026 Tw 1.647 0 Td
(51)Tj
0.109 Tw 8.5 0 0 8.5 469.1566 241.7024 Tm
[( T)-17.7 (he mos)9 (t dr)5.7 (ama)20 (t)-10.8 (ic)26 ( )]TJ
0.053 Tw -18.111 -1.412 Td
[(appr)8.7 (oac)15.6 (h )0.5 (t)15.5 (o )0.5 (im)20.8 (pr)8.6 (o)25.5 (v)26.4 (e )0.5 (t)0.5 (he )0.5 (immuno)9.9 (g)14.2 (enicit)-27.8 (y )0.5 (of g)14.2 (ene)15.7 (t)-10.8 (ic )0.5 (v)23.9 (ac)]TJ
0 Tc 0 Tw (-)Tj
0.026 Tc 0.133 Tw 0 -1.412 Td
[(cine is b)20.4 (y int)-10.8 (r)8.7 (oducin)14.7 (g the pr)8.7 (oper)-23.1 (t)-27.8 (y of \223)4.7 (se)30.4 (lf)20.5 (-r)9.6 (eplic)-5.9 (a)19.9 (t)-10.7 (ion.)32.4 (\224)25.8 ( )]TJ
0.387 Tw 0 -1.412 Td
[(It is ac)13.2 (c)13.7 (om)20.7 (plished b)20.4 (y usin)14.7 (g g)14.2 (ene)0.6 (-enc)13.7 (oded alpha)27.2 (v)-9.7 (ir)-19.7 (us)26.2 ( )]TJ
0.448 Tw 0 -1.412 Td
[(R)-23.6 (N)4.6 (A r)9.6 (eplic)-5.9 (ase)10.9 (, an aut)15.6 (opr)8.6 (o)14.3 (t)13.6 (eol)13.9 (yt)-10.8 (ic pol)13.8 (ypr)8.7 (o)14.2 (t)13.7 (ein, whic)15.6 (h)26.1 ( )]TJ
0.079 Tw 0 -1.412 Td
[(pr)8.6 (omo)14.3 (t)13.6 (e)12.9 (s enor)-15.8 (mous R)-23.6 (N)4.6 (A r)9.6 (eplic)-5.8 (a)19.9 (t)-10.7 (ion in the c)-17.6 (yt)15.6 (oplasm of)26 ( )]TJ
0.152 Tw 0 -1.412 Td
[(inf)24.4 (ec)-13.2 (t)13.6 (ed )0.5 (c)12.2 (e)30.4 (lls)-4.6 (, par)-23.1 (t)-10.8 (ic)-9.7 (ular)11.1 (l)13.8 (y )0.5 (posit)-10.8 (i)14.4 (v)26.3 (e)0.6 (-)19.9 (s)9 (t)-10.8 (r)5.7 (and )0.5 (\223)4.6 (sub)6.2 (g)14.2 (enomic)4.9 (\224)25.8 ( )]TJ
0.186 Tw 0 -1.412 Td
[(mR)-23.6 (N)4.6 (A f)24.4 (or t)0.5 (he enc)13.7 (oded ant)-10.8 (i)22.1 (g)14.2 (en. Ant)-10.8 (i)22.2 (g)14.2 (ens r)9.6 (e)30.4 (le)10.4 (ased fr)8.6 (om)26.3 ( )]TJ
0.214 Tw 0 -1.412 Td
[(the )0.5 (t)-10.8 (r)5.7 (ans)16.4 (f)24.4 (ec)-13.2 (t)13.6 (ed )0.5 (c)12.2 (e)30.4 (lls )0.5 (ar)9.6 (e )0.5 (pr)9.6 (e)12.9 (sent)13.6 (ed )0.5 (t)15.6 (o AP)-6.3 (C)-5 (s )0.5 (t)15.6 (o )0.5 (enhanc)12.2 (e)26.1 ( )]TJ
0.058 Tw 0 -1.412 Td
[(immune r)9.6 (e)12.8 (s)15.3 (ponse v)-9.7 (i)21.2 (a MHC-I c)13.7 (om)20.8 (ple)11.8 (x)-9.9 (, int)13.7 (er)-15.8 (f)24.4 (er)8.7 (on r)9.6 (e)30.4 (le)10.3 (ase)10.8 (,)26.2 ( )]TJ
0.098 Tw 0 -1.412 Td
[(and pr)8.7 (oinf)-55.7 (lamma)20 (t)15.6 (or)-31.9 (y dsR)-23.6 (N)4.6 (A)-17.7 (.)]TJ
-0.026 Tw 4.913 0 0 4.913 437.2881 124.6774 Tm
(47)Tj
0.098 Tw 8.5 0 0 8.5 443.2339 121.7024 Tm
[( T)-17.7 (he nanopar)-23.1 (t)-10.8 (ic)-9.7 (ula)19.9 (t)13.6 (e R)-23.6 (N)4.5 (A)25.9 ( )]TJ
0.96 Tw -15.061 -1.412 Td
[(immuno)14.3 (t)0.5 (her)5.7 (ap)22.8 (y appr)8.6 (oac)15.6 (h int)-10.8 (r)8.7 (oduc)12.2 (ed R)-23.6 (N)4.5 (A)3.8 (-lipople)11.9 (x)25.8 ( )]TJ
0.017 Tw 0 -1.412 Td
[(\(R)-23.6 (N)4.6 (A)3.7 (-LP)11.7 (X)31.8 (\) v)24 (ac)13.2 (cine)10.9 (, enc)13.7 (odin)14.7 (g v)-9.8 (ir)5.7 (al or mut)-6.9 (ant neoant)-10.8 (i)22.2 (g)14.2 (ens)26.2 ( )]TJ
0.096 Tw 0 -1.412 Td
[(or endo)9.9 (g)14.1 (enous se)30.4 (lf)20.5 (-)1.3 (ant)-10.8 (i)22.2 (g)14.2 (ens)-4.7 (, t)15.6 (o induc)12.2 (e s)9 (t)-10.8 (r)8.6 (on)14.7 (g ant)-10.8 (it)-14.7 (umor)25.8 ( )]TJ
0.207 Tw 0 -1.412 Td
[(immune r)9.7 (e)12.8 (s)15.3 (ponse t)13.6 (e)12.8 (s)9 (t)13.7 (ed in a P)16.2 (hase I t)-10.8 (r)-15.8 (i)21.2 (al in ad)13 (v)23.9 (anc)12.2 (ed)25.8 ( )]TJ
-0.026 Tw 0 -1.412 Td
[(me)30.4 (lanoma)-7.8 (.)]TJ
4.913 0 0 4.913 360.5483 64.6774 Tm
(52)Tj
ET
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q
/GS0 gs
0 TL/Fm0 Do
Q
BT
0 0 0 1 k
/GS1 gs
/TT0 1 Tf
0.01 Tc -0.01 Tw 9 0 0 9 548.2205 763.6535 Tm
(323)Tj
ET
q
0 Tc 0 Tw 0 g
/GS0 gs
0 TL/Fm1 Do
Q
BT
/TT1 1 Tf
0.02 Tc -0.02 Tw 11 0 0 11 51.0236 731.7566 Tm
[(C)6.6 (onc)8.6 (lusion)]TJ
/TT2 1 Tf
0 Tc 0.204 Tw 8.5 0 0 8.5 51.0236 713.7566 Tm
[(T)-17.7 (her)5.9 (apeut)-11 (ic c)-5.8 (anc)12.2 (er v)23.9 (ac)13.1 (cine)13.1 (s le)10.5 (ad )-0.6 (t)15.5 (o ac)-13.3 (t)-10.8 (i)14.4 (v)23.9 (a)20 (t)-10.8 (ion of immune )]TJ
0.176 Tw 0 -1.412 Td
[(memor)-31.2 (y t)0.5 (ha)20 (t is lon)14.9 (g las)9.1 (t)-10.8 (in)14.9 (g)1 (, s)2.1 (af)24.3 (e)10.9 (, and e)23.1 (f)-14.2 (f)24.4 (ec)-13 (t)-10.8 (i)14.3 (v)26.4 (e and henc)12.4 (e )]TJ
0.573 Tw 0 -1.412 Td
[(has bec)13.7 (ome )0.7 (an a)19.9 (t)-18.1 (t)-10.8 (r)5.8 (ac)-13.3 (t)-10.8 (i)14.4 (v)26.3 (e me)16 (thod of immuno)14.9 (t)0.5 (her)5.8 (ap)22.8 (y)48 (. )]TJ
0.288 Tw 0 -1.412 Td
[(T)85.8 (umor-)20 (s)15.4 (pecif)-32.6 (ic neoant)-10.5 (i)22.2 (g)14.1 (ens )0.7 (tha)20 (t ha)27.3 (v)26.4 (e the lo)25.7 (w)26.5 (e)12.8 (s)9 (t r)-15.8 (is)25.8 (k)-10 (s )0.5 (of )]TJ
0.432 Tw 0 -1.412 Td
[(aut)15.4 (oimmunit)-26.9 (y ar)9.5 (e pr)9.5 (e)23 (f)24.4 (er)-15.6 (r)9.6 (ed ther)5.8 (apeut)-11 (ic t)-6.9 (ar)1.3 (g)14.2 (e)15.7 (t)-7.4 (s f)24.4 (or the )]TJ
0.021 Tw 0 -1.412 Td
[(de)18 (v)26.4 (e)30.3 (lopment )0.5 (of c)-5.9 (anc)12.2 (er v)23.9 (ac)13.1 (cine)11.1 (. Alt)0.5 (hou)21.1 (g)-1.5 (h man)29.6 (y pr)9.5 (e)18.2 (v)-9.8 (ious t)-10.8 (r)-15.8 (i)]TJ
0 Tw 27.335 0 Td
(-)Tj
0.101 Tw -27.335 -1.412 Td
[(als of t)0.5 (her)5.8 (apeut)-10.9 (ic c)-5.9 (anc)12.2 (er v)23.9 (ac)13.1 (cine)13.1 (s f)16.1 (ailed t)15.6 (o sho)25.8 (w pr)8.5 (omisin)15.6 (g )]TJ
-0.005 Tw 0 -1.412 Td
[(r)9.6 (e)12.8 (sult)-7.1 (s)-4.6 (, c)-9.8 (ur)-15.8 (r)9.6 (entl)14 (y se)18.4 (v)26.4 (er)5.8 (al on)14.7 (g)13.2 (oin)15 (g s)9 (t)-14.7 (udie)12.7 (s ha)27.3 (v)26.4 (e been sho)25.7 (w)-7.7 (in)14.9 (g )]TJ
0 Tw 0 -1.412 Td
[(a)20 (t)-18.2 (t)-10.8 (r)5.8 (ac)-13.3 (t)-10.8 (i)14.4 (v)26.3 (e c)15.8 (linic)-5.3 (al out)14.3 (c)13.6 (ome)13.2 (s)-4.7 (.)]TJ
-0.041 Tw 1.334 -1.412 Td
[(In )0.5 (addit)-11.1 (ion, )0.9 (a c)13.7 (ombina)20.1 (t)-10.8 (ion )0.8 (of )0.6 (ICIs)-4.9 (, c)15.7 (hemo)14.6 (t)0.5 (her)5.8 (ap)22.8 (y)48 (, )0.6 (or r)5.7 (adio)]TJ
0 Tw 26.001 0 Td
(-)Tj
0.096 Tw -27.335 -1.412 Td
[(ther)5.9 (ap)22.8 (y w)-7.7 (it)0.6 (h c)-5.8 (anc)12.2 (er v)23.9 (ac)13.1 (cine)13.1 (s )0.5 (tha)20 (t r)9.6 (e)18.2 (v)26.4 (erse )0.6 (immunosuppr)10.2 (e)12.8 (s)]TJ
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(-)Tj
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[(Ins)9 (t 2009;101\(19\):1348\2261355)]TJ
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(14)Tj
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EMC
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0.337 Tw -1.965 -1.361 Td
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EMC
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0 Tc 0 Tw (-)Tj
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(16)Tj
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EMC
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EMC
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