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`Editor-in-Chief
`Kenneth C. Anderson
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`Dapuw Editors
`15:11“ L. Abbruzzese
`“ll 95 l.. Arleaga
`I ham ii. Barlow
`lSusan ii. Bates
`[Slander R. (:randis
`pnc-l‘l. Rubin
`aincia S. Sieeg
`
`
`
`Clinical
`Cancer
`Research
`
`The Journal of Clinical and Translational Research
`
`Robert 1.. I'erris
`Holdano l-‘errone
`William I).
`|-'igg
`Richard .‘i. I"inn
`M irhelangelo I-‘iormlinu
`Antonio '|‘. linio
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`Publishing
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`Clinical
`Cancer
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`The Journal of Clinical and Translational Research
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`l'tilit\«I
`
`Nu rcsiittiisthilily is .iut-pit-tl liy tlit- I-'.t|ltni-s III
`by AMZII. liit. llll' Ilic tipiniiilts i'spit'sst'tl I‘iv
`t'tiiitrlhtitnrs tir I'tir tlit- ttiiitt-iil til' ll'll'
`.ltlvl'f‘llSl‘lflt’llifi.
`
`Mitt-titan Assotiiitiuli ltir (..iittci' Nt'\l'tll'lll
`til "i (Ilii s tllIl .‘iltt‘t'l
`|'|iil-itlt'|]i|ii.i. £'r\
`l‘.| IIIt. -I-llI-l
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`lax. )1“: -l-ltl 'it'i-I
`
`i
`iti.ti1:
`li'llf£-'.
`II III}:
`Wt'ii‘tilt': wwtv..t.it mitt.
`
`
`Clinical Research
`jflC{.-Iiimi'it'titi :iuurriiriiiri {or Cmicechsearcli
`
`

`

`Contents
`
`Clinical
`Cancer
`Research
`The Journal of Clinical and Translational Research
`
`January 15. 2013 - Volume 19 0 Number 2
`
`Highlights of This Issue 309
`
`CANCER THERAPY: PRECLINICAL
`
`EATURES
`SPECIAL F
`-
`_
`OCR Translations
`311
`'I'nrgclcd Isulrelinoin in
`. |
`_
`t _
`Nelll'tlhlmilomu: K'
`II' ,.
`i‘l)§t)rp|i0n
`m1 In». (undies. or
`Katherine K. Maltl'rw
`5w ‘lrfll‘ha" .0. 4(19'
`
`S
`
`314
`
`Bus
`
`tatistics in Clinical Can cer ResearCh
`'
`‘
`.
`',"""'r Bum?“ Madelmg Versus
`LNSI‘FSSIK'n'1:rec Survival for mm“ It
`I“. ],_ll?:liwra mg
`
`‘
`
`|
`
`I
`
`MOIECLflaf Pathways
`320
`Muleculnr Palhways: Comparing the
`#3312? of lzrllgs and T Cells in
`I
`c Ive y
`“’5‘"_0flcogelies
`killlllt'lfll Anders and I’lmlnns lllnnkenslein
`
`REView
`327
`
`-
`The Role. nl‘JAK Pathway
`'lysrvsulalion in ""3 Palllngenesis and
`1 reatmenl "f Ac"“3 Myeleid lfiukt'lllia
`I‘lun ,Iu lee. Naval Havel: lineup M. Kunlurjiun.
`Fal'dan \-(-r5lt)\'5(uk. and |-':Irh:n| lim'amli
`
`335
`
`HU A
`M N CANCER BIOLOGY
`..
`lemon] Lymphocytic lnl'illralien and
`Expressinn of the (Themokine CXCIJI]
`in Breast Cancers from the Ontario
`Familial llreasl Cancer Registry
`Anna Marie Mulligan. Irene Ilailmam.
`I.inl|:l Fuck-y. Iluslulllthi I’innaulllwngt‘.
`[.inh 'l'. Nguyen. Frances l‘. [l'Mnllmx
`Pamela S. Uhilshi. and Irene |.. .‘hllI-rulis
`
`347
`
`357
`
`367
`
`380
`
`393
`
`Milaluaumali—Ceningalcd Liposemes
`as Targeted Ilexametllasene Carriers
`for Therapeutic Delivery in (3074'
`It-ccll Malignancies
`Vii-hemp. Man. (heel-gin 'I'rinnlallilltm.
`Erin llerllein. William Towns.
`Mullhew Steliinm'ski. Xiamkui Mn.
`limit! jurinurai. Milt'll Phelps. [illitltl Mun-uu-i,
`ly lumes Lee. David M. (inldenherg
`Robert _|. Lee. Julm C. Byrd. ilIlLl
`Nuluruiaul Mulliusumy
`IIMS-‘J3656IUMDX-I338: A Fully
`Human 1nli-CXCII4 Alllihed Induces
`Apoptnsis In Wire and Shows;
`Antilumor Activily In Viva in
`Hematologic Malignancies
`Michelle ll. Kulme. 'l'unyn Millet-y.
`lilnke lielangel: Sharline {‘hen. Chin l'nn.
`
`:"I'
`
`Karla A. Meaning. Lewis j. (.‘uhen.
`a
`.'
`;.a
`"l
`'l.‘
`
`('ulint'lmng. Fei ('au. Walla Niekl'n. 'l‘nm Kt‘mpe.
`A1 u: _]
`iwrnnn Iml | In I h
`(uril III.
`||
`In Wire Sensitivity of Clal: Cells In
`Fludtlrflbine May Be Modlllaled by the
`Stimulation “f Toll-like Receptors
`l-Ilt-unnru anle. Hem-dell“ .-\pnllnnin.
`Lydia: Seal-III. l‘nmeln llalngllelli. Claudia Hui.
`[‘nnle (lliia. Federica ('aliguI'is-(‘nppiu and
`M;
`'l:
`.\|
`“ l
`[mu
`c-Sre Activation Mediates Iirlolinib
`Resistance in Head and Neck Cancer by
`Slimlllalitlg c-Mel
`1mm! p_ Slalhilt'. Gunning He.
`Vivian Wui ‘i'an |.ui. Cassandra Ill'lll’};
`Christopher T. Ulihish. Sunnli lnyre.
`Kelly M. Quesnelle. Ilill M. Siegfried. and
`Jennifer ll. (irantlis
`“IMF Inhibition Increases 'I‘nmnr
`Infiltralinn by T cells and Enhances
`the Anlilumor Activity of Adaptive.
`lmmunetherapy in Mice
`('liengwen |.iu. \‘L’eiyi l’eng. (‘Iinnyu Nu.
`‘I'anynn Lou. Minying Zlmng._lennilbr A. Wurgu.
`lie {ling {‘ln‘n. llniynn S. Li.
`Stephanie H. Wailuwieh. Yam ‘i'nng.
`[Jennie ‘I'mupem Fl'etlerit'k. Zul'lnll'y .-‘\. [’unper.
`llinu M. lt-lhufung. Mayra \-\'l1illinglnn.
`Keilll 'I'. l’lailierly. Senll
`|".. \-\-’umlmun.
`Mirlnu-l .-\. I'mvies. Lassie ti. llmlmnyi.
`\‘i'illem W. Urem'iik. (iregon' Lizee. and
`l'alriek llwn
`
`___________________________————-
`slatlcnal Research
`ii‘
`‘
`The Journal of Clinical and Tran
`‘
`Fins material wascnpled
`aacnouma'S-mg
`_
`I
`WWW.
`attl'te NLM and may be
`Subject USOopvyright Laws
`
`

`

`
`
`404
`
`415
`
`428
`
`I’ll“ lnIIihilors Synergislieally
`l’olenliale "Us“: lnllihilor I.elllalily
`
`in lmalinih Mesylale—Se
`live or
`—Ilesislanl litililr\lll.'
`1.1. lkemia
`Cells In l-‘r‘l'ro and In Vim
`(jiri'pu Ilusrnzllmpuiru.
`ilirzll I’alel. Tr": Nguyen.
`I'llisn .-\IIki.~.-5.un.;1nd Slew" (Irunl
`
`Complete Regression of Melaslalil‘
`
`Ilenal (Iell Carcim In by Mulliple
`Inieelions of Engineered
`Mesenellymal Silem Cells Expressing
`l)mlecamerie 'I‘llnll. and HSV—TK
`Sm- \\-'m1 Kim. “in Iin Kim. Sung; linoo I’ur'k.
`Ilylln (illl Yang..\Io(:n('|1eol Rang.
`Young Won {'llni. Swing. kink Kim,
`Sin-Sm: Jenn, :mtl \'nln1g_=.('|1uf Suns,
`
`Dysreglllalion ol IIIe Ilepressive
`"31(27 'l'rirm-lhylalion Mark in Ileatl
`aml Neck Squamous Cell Carcinoma
`('onirihules lo llysregulaled
`Squamous llillt-renliillitlll
`(II'Iu M. (imlllon. Lilia Meridu Ile lung.
`|.i|i;m:l limit: Munoz.
`.\|ehlik;l Iluzzu‘ lielhillum. :uul
`Xil'holils .\. Saunders
`
`CANCER THERAPY: CLINICAL
`
`45?.
`
`Durable l'aueer Regression ("I'-
`'l'realulem and l-Zl'l‘eelive Ileimluelioll
`
`459
`
`Tin-rap} will! an I"I'IIi-Il]’-l Antibody
`l-.\':!I1_I. film-n. \‘I'illium II. Hllul'fllunl.
`t'lrurles I I. ”rate. lru WuIIIIr-I'. Innis M. '1 :mlle.
`Iiolwr1 .-\.
`.‘unlera. ”airing XII. Ellen}; ‘I'nn.
`Mire Pom. Liepinp, ('Iu-rl. Drew .\1_ l'ul‘rloll.
`Illlll’ Ii. “I'IIIIIIII'I'. uml HIIfllllm'
`|.. 'I'npnliun
`
`Iltlaplive Dosing Approaches lo the
`lndividualizalion ol' lil-(‘is-Ilelinuie
`
`Acid [lsolre
`n) 'I'realmenl for
`(Children will: High-Risk
`Neurohlasloma
`(iill't'llIJ. Yin-II. lulie I’I'I'inglno.
`Sophie I’.. Howlmflmm. Nil-”In .‘I. lliiugwurlln.
`(Sluulu .\I:L|ik. Mit'luu-l ('ule. .-\r1|1 |\'.
`|Ju|_\'.
`.-\mlrm\ Il.l. I't’arsnn. ulul .-\|-.|II \'. Ill::|:|_\'
`.‘w'er' mmnn'nmr'jn p. H I
`
`PREDICTIVE BIOMARKEHS AND
`PERSONALIZED MEDICINE
`
`IMAGING, DIAGNOSIS, PROGNOSIS
`
`442
`
`Varialion in Precursor Lesions of
`
`Pancreatic Cancer among High—Risk
`Groups
`'J'IIIIITIJIH I]. I'Uljl'r'. III-ruiil.‘u'lIIII.I'1-1erI..|II_-_::-r.
`IIIIIJIIIIH": 'l _
`I II‘H'I'IIIIIL'J'II. Mum” \.|..\I. \\.N.I‘I'.
`I'.I]Ii|_\'
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`."llII'I'l‘iIII. “I‘I'I.
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`MHIIIIIIH Hillgi'llu.
`IIIHIIIIIH .\|. lull'H".
`IL'IIIKl'..\.\il'1l'll..lllllIll'lll'lh Hurt-u II
`I1:-I|.'|I| III IIII‘ I [-uII'n I
`.IJIIIIIJIJ I'.IIH Il‘illll
`[lump .Iml [he I
`.II'.II .|
`|l"_"|'1|l'\
`
`:III
`illH'l'l
`
`l
`
`450
`
`I’rognoslie Significance of .-\I\"l';‘
`m'l'llll and .\l.-\l’l\' Pathway-a aml
`I‘llllilumor l-‘Il‘eel of m'l'llll lnllilailol'
`in Nl-‘l-llelnlell aml Spol'mlie
`Malignant Peripheral Nerve Sllealll
`"I‘unmrs
`\I;1Lu|n I rlllo. Ililll'lilkil LIIHIIIIHIIH.
`\nLiluLu 5mm. kt'rllt'lll kulmulli.
`‘Ilhukv Inkulmkhi.
`lullxl'illnl
`l‘iilll.
`Lei it'lmu IiIIH. ‘Iusllillir'll Millfillllmlu.
`Kljl'lliIIII-I'I ”ulna/HM.
`.\|ikikl: I‘.!Jixl.
`”Il'tl‘illl Imwlki. Yul: Hohushi.
`Kellirhi \inlliyuum. I'Irkillitll- Iu'aunolu. uml
`Ymhiliuo (III-.I
`
`480
`
`491
`
`lleleelion of Novel f‘cliflllilllll. Hem-lie
`Changes in Salivary l)uel Carcinoma
`llelps Ilireel l’alielll 'l'realmenl
`\'z|.|e|1lin;l Xurdi. I'I'll'l' M. Hutluw. Ileiml Iurie.
`Iliu'e'1'.h;lu..-\I'jul:l K.{'o~;per.Krislin Helgetllnu.
`Vanessa |.. Sriululllnu. lulie M. Hullen.
`IJurrell II. Burger. :‘IIIIIII:1I_\'_III|I:I
`|:II'i':Il<-_
`"l'lll’l'i'fl S. lieisl. llunuld I'.
`|.;u\'rem'e.
`Keilh 'I.
`|-'|:I|II-I'I3.'. Inllurmu ('. Ilelulell.
`Ilnlliel Ilt'HI'IIIUI'. ‘I'i 1.i. Lori I, \\'i1'l||. :Ind
`Iloru |Ji:|s-H;mlal;.::llu
`
`Iulegralion ol' (‘ell Line and {'Iinieal
`'l'rial (ienome- Wide Analyses
`Supporls a l'olygenie Arehileelure ol‘
`I’aelilaxel—Induced Sensory
`Peripheral Neuropalhy
`lll‘llllll'l'
`|-.. \\'|Iel'|er. l-II‘ir II. {lama/ml.
`('Inmliu hing. l
`:‘IIl’IIIIH [1. Mini”.
`(‘ltullunlnrn .\"|uLII: lluherl Mirllau-I linltlnill.
`Ixoolmiln 1::1'. ['Iu-n Jinug. Ilorulhy Wuhan.
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`III:
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`.\I'.ll'l\
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`l'.|II[l'l .nnl Lrulnenun {Il'llllll II: Nunu J.
`t m.
`.mll \I.I|\'
`i-Ilr-eu III-Ln:
`
`[Ki Imrr u rm .-| um mm” Jim ffam‘r'rRr'wrm'h
`
`
`iv
`Clinical Cancer Research
`This material wasccpied
`at the HIM and may be
`Subject us might Laws
`
`

`

`_—___—____——_——__—___._—_———
`
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`Hm ‘JUtlllTill 0| Clnnntnl and Tmnslzltionnl Research
`_
`_
`v
`_
`This material wascapled
`at the NLM and may be
`Subject US Copyright Laws
`
`

`

` This material may be protected by Copyright law (Title 17 U.S. Code)
`
`Cancer Therapy: Clinical
`
`Research
`
`Gllnlcal
`Cancer
`
`Durable Cancer Regression Off-Treatment and Effective
`
`Reinduction Therapy with an Anti-PD-1 Antibody
`
`Evan J- Lipson‘. William H. Sharimanl'a, Charles G. Drake”, Ira Wollnerfi. Janis M. Taube3"".
`Robert A. Anders”. Haiying Xu’l. Sheng Yao”. Alice Pone‘. Lieping Chen”. Drew M. Pardoll‘.
`Julie R. Brahmer'. and Suzanne L. Topalian“
`
`Abstract
`
`1 antibody
`Purpose: Results hour the lirst-in-htrmatt phasel trial ol'theattti-progranrmetl death-l {l’li- |
`BMS-‘Hhfififi in patients with treattrtenl—rel'rat'tory solid tumors. including salety. tolet'ahility. pharmaeo-
`dynamit's. and immunologic" t'orrelates, have heett previously reported, I lei'e. we provide long-term follow
`up on three patients from that trial who sustained ohiet'tive tumor regressions oil therapy, and test the
`|Whothesis that reindttetiml llll'l'dl"? for late tumor reenrrent'e ean he elleetive.
`Experimental Design: 'I'hree patients with t'oloreetal t'aneet’. renal t'ell eant'er, and melanoma at'ltieved
`
`ohieetive responses on an intermittent dosing regimen of HMS-‘J “3558. Following cessation ol' therapy.
`patients were lollowed for more than ’i years. A patient with melanoma who experienced a prolonged partial
`regression followed hy ttrmor reeut'rent'e rereiyed reinduetion therapy.
`
`Results: A patient with eoloreetal t'aneerexpet'ieneed a eomplele response. whieh is ougoingalter iyears.
`A patient with renal t'ell ('attt'erexperietrt'ed a partial response lasting E years ol'i'therapy, whieh t'onverled to
`a eomplete response, whit'h is ongoing at 12 months. A patient with melanoma aehieved a partial response
`that was stahle for 1 ti months ol'l' therapy; reenrrent disease was sttr't'esslitlly treated with reindut'tion anti-
`l’ll-l therapy
`
`Conclusion: these data represent the most prolonged observation to date ol'patienls with solid tutttors
`responding to anti H H irumtinothetape arid the first report ol'sut't'esslttl reindttetion therapy following
`delayed tumor progression. 'l'ht‘y ttttdt'tst (”'1' the potential Iiil' itttltrttne t het'ltpoiltt hlot'ltade with altti-I’i )-|
`to reset the eutrililrr'iutn helm-err tumor and the ltost immune system. tfliutfttrtt'et' lies; WU): it’d-ti. ‘I'IJr‘iiJ
`doll 'li.
`
`lrrlrorit ttgtroit
`
`ihe spec iltr or selettiyt' expression HI atrlttgetrs l)_\’ i. din er
`tells t. r't.'.ttr's an opportunity IIII t‘Ittit I11t'tttitrs tell Illt'tlltllt'tl
`and serologir
`itunrttut- attat It and lot
`intuutruitlieraperrtit
`interventions.
`lhe tll'\'l‘ltl|illlt‘lll ol ellt-t'tiye rant et
`itttrutt
`Ittitltt'tapies depends on t't'yt'tsltu: |IIlili>lllll}-’ arid loleto
`genie signals iii
`the tumor outroenyuoritrieut.
`therehy
`enhantitrr;
`the yisihility ol
`tumor tells to the immune
`syslt'ttt.
`lit
`the last detade.
`it has ltt‘ttuut' clear
`that
`the
`
`'[Jerinnmtn
`Authors' Affiliations: Depatttnenlsol 'Oocology. ”Urology,
`gy. "Pathology. and "Surgery. Johns I-toukrns Untyersrty School nl Mod
`tome and Sidney Ktntnrel Compiehensrye Cancer Center, Bfllllr'llm'FL Many.
`land; and'lDepadmcut of internal Medicine. Wayne State Unwersrty School
`ol Medictne and Henry Ford Hospital. Detroit. Michigan
`
`Current address for S. Yao and L. Chen: Department at lrnrnunobt‘ology.
`Yale Universrty. New Haven. CT 06519.
`
`Corresponding Author: Evan J. Lipson. Department ot Oncology. Johns
`Hopkins University School or Medicine and Sidney Kirrirnel Comprehensive
`Cancer Center. 1550 Orleans Street. David H. Koch Cancer Research
`Building, Baltirtrore. MD 2128?. Phone: 410-502-8200; Fax: 410-502-
`1958: Email: eyenlipsonfifljhmiedu; and Suzanne L. Topalian. E-mail:
`stopati‘tfirihmiedu
`deli: 10.1lSBr’lD?8-0432.CCR-l2-2525
`' 201? American Assocration for Cancer Research.
`
`iltttttttrte regulatory pathway t'titnptrsed til' Drugt'attrnred
`death-l {pt}. I. {j|)37*J], .r ret'epttir' expressed on .tt'livaled
`'l'anti lit'ellsaud itsligands l’l it! (It? II], t It }J7rllaml |’| )-
`|..J [ll'F-IHL. (LINN), plays an integral role in the down
`modulation ol antitumot'
`immunity.
`ltrhihition Hi
`this
`pathway ttsittg hlot'kinp,
`triorrorlortal antibodies {mAIi}
`against Pl! 1 or l’l) H is emerging as .tn el'l'et rive method
`In: reversing:arttt‘l' itIttItttIttrsllppr'essirilt .rrttl Ihereliy t. .ttts
`my. tumor repression in patients with .rtlvantetl disease ( l l.
`Although snt h therapies are still in development. they have
`shown protrrisiny. : linir al results not only hit tumors tlas
`sitally tonsitlered to he immunorteni: stttlt .ts melanoma
`and renal
`tell carcinoma [ltt.t.]. hut also lor tomntott
`epithelial rualiitnant it-s sot h as Itltlt - small I ell him; I anrer
`{NStLItJ}, historit ally resistant to itntnnnotherapy.
`HMS-‘1 iti'iril‘i {MHX I Illhfl 1N” -l"i it‘ll
`is
`.1 hit): ltit‘tp‘
`matr spet'ilit
`lot
`ltttluart
`I’IJ I. The llt'sl irt httItIart single
`dose. dose-t'st'alatitllt tt'ial ol'tllis agent reported lly lilahttter
`atttl
`ttilieagties {.3} enrolled i') paliettts will!
`ttealtttetrt
`r't'lr'atltrl'y tnetaslalit solid tumors itttlttdittt; ttielalttitrra.
`lttiti, t'oloret'taltamer l( th( I]. NSt it
`t
`1. and t'astralion resis
`tant prostate t'dllt't'l [t lltl’t T}. A layotahle salety prolile and
`preliminary (‘Vltlt‘llt't' ol' t'linital .tt'tivity in all histologit-s
`except (Illl‘tl
`led It!
`the design til
`.1
`Itrttllitlttst'
`trial ol
`
`462
`
`
`Clin Cancer Res; 19(2) January 15. 2013
`
`mC-1. Imi'trrttrr. IHIN trilrrui lt'rtt t“Imm't'Resrrtreh
`
`This material wascopied
`at the NLM and may be
`Subject US Copyright: Laws
`
`

`

`Durable Response and Effective Fleinduction with Anti—PD—t mAb
`
`Translational Relevance
`
`This report provides long-term lollow-ttp on patients
`from the lirst-irt-human trial ol' the anti—I’D-l antihody
`liMH—‘J {(9158 (MDX-l too} who aehieved (thieetive I
`tumor regressions. 'l'hey inelude patients witlt metastatic
`melanoma. eoloreetal. and renal t'atteer. Remarltahly,
`dttrahle responses int'ludingt'ontirtued tumor regression
`ol‘i' therapy were ohserved. Iv'urtltertttore. a patient with
`melanoma. who esperieneed ttrmor recurrenre follow—
`ing a prolonged partial response. responded to reinduc-
`tion with anti-l’lll therapy, 'l‘ltese findings oi‘durahle
`treatment elleet underscore the potential for immune-
`hased therapies such as antihodies hloeking the immu—
`nosut‘ipressive l’D—lfl‘l)—l.1 pathway to reset the equi-
`librium between tumor and the host immune system,
`distinguishing them from eonventional chemotherapies
`as well as small—molerule inhibitors of oneogenie driver
`pathways. 'l'hey represent the most prolonged observa-
`tion of patients with solid tumors responding to anti-
`|’l)-l immunotherapy to date, and the first evidence that
`reindttt'tion therapy with this agent after late tumor
`reeurrent'e may he eiiet'tin‘.
`
`
`
`
`
`.
`
`ltMS-‘t limits in 3% patients that was ret'ently reported ( l).
`tonlittning .mtitutuor ellit'aey in melanoma.
`lttitl. and
`NS( II .( ..
`
`'l lit-adaptive immune systeru has a vastt'apat'ity l'orspet'iiit'
`antigen retognition and holds the potential
`to adittst
`to
`ongoing Itunor evolution, inelnding genetit' and epigenetit'
`thanges that
`Iypieally tanse resistant‘e to small-Inolet'ttle
`inhihitt n's.'l'liis adaptaltilily. t'oupled with an immune ment-
`my t'otnpont'nt. itttplies that itntnttnolitet'apyt'att "I'L‘ot'iettt"
`endogenous atttitntnor immunity with dnr-ahle eliet‘ts even
`alter the cessation or therapy Here. we provide long-term
`lollow-up on patiettts l'rom the lirst-in-htunan trial ol' Ills-is-
`‘t lirfi'Rl-i who .tt'hievetl trl‘iit‘t'livt' tttmttr regressions. int'lttdittg
`a patient with (Silt: who maintained a t'omplete response
`it IR) oll' therapy.- a patient with R( I '. who sustained a partial
`response [I'll] that t'ottvel'ied to a t'.R oli therapy; and a
`patient with melanoma who experient'ed a prolonged I’ll ol'l'
`therapy lollowed hy tuntor progression and their response to
`reindut'tion therapy with the same anti-l’l'l-l antihody.'l'hese
`data represent the most prolonged ohservation oi' patients
`with solitl tumors responding to .utti-l‘ll-l therapy and the
`first evident'e that reindttetion therapy with this agent al'ter
`late tumor progression ma)’ he L‘llt‘t'lth‘. the observed dura-
`hility ol responses underst'ores the potential for immune
`tltt‘t ltpoittt lilttt'ltadt‘ with anti-l‘l l-I to reset the t‘qttililtt'ittlt‘t
`hetween tttmor and host and provide durahle tumor t'ontrol
`alter cessation oi therapy.
`
`Materials and Methods
`
`'l‘reatments administered and response evaluation
`HMS 'Jttts'itt.al'nllyhumaoinnntmoglolmlin(i=1{1g(i-i]
`ltltll Ling In.-\h against H H, was administered in a multi'
`
`institutional. lit'sl-itI-lttllttatt, phase I tlose-est'alatitm study
`{3}. The protot'ol was approved hy lot'al
`Institutional
`Review littat'tls {Hill},
`.tttd all pat'tit'ipalittg sttltiet'ts signed
`inl'ormed t'onsent.
`'l‘he .tntihody