31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016): part two
نویسندگان
- Casey Ager
- Matthew Reilley
- Courtney Nicholas
- Todd Bartkowiak
- Ashvin Jaiswal
- Michael Curran
- Tina C. Albershardt
- Anshika Bajaj
- Jacob F. Archer
- Rebecca S. Reeves
- Lisa Y. Ngo
- Peter Berglund
- Jan ter Meulen
- Caroline Denis
- Hormas Ghadially
- Thomas Arnoux
- Fabien Chanuc
- Nicolas Fuseri
- Robert W. Wilkinson
- Nicolai Wagtmann
- Yannis Morel
- Pascale Andre
- Michael B. Atkins
- Matteo S. Carlino
- Antoni Ribas
- John A. Thompson
- Toni K. Choueiri
- F. Stephen Hodi
- Wen-Jen Hwu
- David F. McDermott
- Victoria Atkinson
- Jonathan S. Cebon
- Bernie Fitzharris
- Michael B. Jameson
- Catriona McNeil
- Andrew G. Hill
- Eric Mangin
- Malidi Ahamadi
- Marianne van Vugt
- Mariëlle van Zutphen
- Nageatte Ibrahim
- Georgina V. Long
- Robyn Gartrell
- Zoe Blake
- Ines Simoes
- Yichun Fu
- Takuro Saito
- Yingzhi Qian
- Yan Lu
- Yvonne M. Saenger
- Sadna Budhu
- Olivier De Henau
- Roberta Zappasodi
- Kyle Schlunegger
- Bruce Freimark
- Jeff Hutchins
- Christopher A. Barker
- Jedd D. Wolchok
- Taha Merghoub
- Elena Burova
- Omaira Allbritton
- Peter Hong
- Jie Dai
- Jerry Pei
- Matt Liu
- Joel Kantrowitz
- Venus Lai
- William Poueymirou
- Douglas MacDonald
- Ella Ioffe
- Markus Mohrs
- William Olson
- Gavin Thurston
- Cristian Capasso
- Federica Frascaro
- Sara Carpi
- Siri Tähtinen
- Sara Feola
- Manlio Fusciello
- Karita Peltonen
- Beatriz Martins
- Madeleine Sjöberg
- Sari Pesonen
- Tuuli Ranki
- Lukasz Kyruk
- Erkko Ylösmäki
- Vincenzo Cerullo
- Fabio Cerignoli
- Biao Xi
- Garret Guenther
- Naichen Yu
- Lincoln Muir
- Leyna Zhao
- Yama Abassi
- Víctor Cervera-Carrascón
- Mikko Siurala
- João Santos
- Riikka Havunen
- Suvi Parviainen
- Akseli Hemminki
- Angus Dalgleish
- Satvinder Mudan
- Mark DeBenedette
- Ana Plachco
- Alicia Gamble
- Elizabeth W. Grogan
- John Krisko
- Irina Tcherepanova
- Charles Nicolette
- Pooja Dhupkar
- Ling Yu
- Eugenie S. Kleinerman
- Nancy Gordon
- Italia Grenga
- Lauren Lepone
- Sofia Gameiro
- Karin M. Knudson
- Massimo Fantini
- Kwong Tsang
- James Hodge
- Renee Donahue
- Jeffrey Schlom
- Elizabeth Evans
- Holm Bussler
- Crystal Mallow
- Christine Reilly
- Sebold Torno
- Maria Scrivens
- Cathie Foster
- Alan Howell
- Leslie Balch
- Alyssa Knapp
- John E. Leonard
- Mark Paris
- Terry Fisher
- Siwen Hu-Lieskovan
- Ernest Smith
- Maurice Zauderer
- William Fogler
- Marilyn Franklin
- Matt Thayer
- Dan Saims
- John L. Magnani
- Jian Gong
- Michael Gray
- Jeff Hutchins
- Bruce Freimark
- George Fromm
- Suresh de Silva
- Louise Giffin
- Xin Xu
- Jason Rose
- Taylor H. Schreiber
- Massimo Fantini
- Sofia R. Gameiro
- Karin M. Knudson
- Paul E. Clavijo
- Clint T. Allen
- Renee Donahue
- Lauren Lepone
- Italia Grenga
- James W. Hodge
- Kwong Y. Tsang
- Jeffrey Schlom
- Jane Grogan
- Nicholas Manieri
- Eugene Chiang
- Patrick Caplazi
- Mahesh Yadav
- Patrick Hagner
- Hsiling Chiu
- Michelle Waldman
- Anke Klippel
- Anjan Thakurta
- Michael Pourdehnad
- Anita Gandhi
- Ian Henrich
- Laura Quick
- Rob Young
- Margaret Chou
- Andrew Hotson
- Stephen Willingham
- Po Ho
- Carmen Choy
- Ginna Laport
- Ian McCaffery
- Richard Miller
- Kimberly A. Tipton
- Kenneth R. Wong
- Victoria Singson
- Chihunt Wong
- Chanty Chan
- Yuanhiu Huang
- Shouchun Liu
- Jennifer H. Richardson
- W. Michael Kavanaugh
- James West
- Bryan A. Irving
- Ritika Jaini
- Matthew Loya
- Charis Eng
- Melissa L. Johnson
- Alex A. Adjei
- Mateusz Opyrchal
- Suresh Ramalingam
- Pasi A. Janne
- George Dominguez
- Dmitry Gabrilovich
- Laura de Leon
- Jeannette Hasapidis
- Scott J. Diede
- Peter Ordentlich
- Scott Cruickshank
- Michael L. Meyers
- Matthew D. Hellmann
- Pawel Kalinski
- Amer Zureikat
- Robert Edwards
- Ravi Muthuswamy
- Nataša Obermajer
- Julie Urban
- Lisa H. Butterfield
- William Gooding
- Herbert Zeh
- David Bartlett
- Olga Zubkova
- Larissa Agapova
- Marina Kapralova
- Liudmila Krasovskaia
- Armen Ovsepyan
- Maxim Lykov
- Artem Eremeev
- Vladimir Bokovanov
- Olga Grigoryeva
- Andrey Karpov
- Sergey Ruchko
- Alexandr Shuster
- Danny N. Khalil
- Luis Felipe Campesato
- Yanyun Li
- Taha Merghoub
- Jedd D. Wolchok
- Adam S. Lazorchak
- Troy D. Patterson
- Yueyun Ding
- Pottayil Sasikumar
- Naremaddepalli Sudarshan
- Nagaraj Gowda
- Raghuveer Ramachandra
- Dodheri Samiulla
- Sanjeev Giri
- Rajesh Eswarappa
- Murali Ramachandra
- David Tuck
- Timothy Wyant
- Jasmin Leshem
- Xiu-fen Liu
- Tapan Bera
- Masaki Terabe
- Birgit Bossenmaier
- Gerhard Niederfellner
- Yoram Reiter
- Ira Pastan
- Leiming Xia
- Yang Xia
- Yangyang Hu
- Yi Wang
- Yangyi Bao
- Fu Dai
- Shiang Huang
- Elaine Hurt
- Robert E. Hollingsworth
- Lawrence G. Lum
- Alfred E. Chang
- Max S. Wicha
- Qiao Li
- Thomas Mace
- Neil Makhijani
- Erin Talbert
- Gregory Young
- Denis Guttridge
- Darwin Conwell
- Gregory B. Lesinski
- Rodney JM Macedo Gonzales
- Austin P. Huffman
- Ximi K. Wang
- Ran Reshef
- Andy MacKinnon
- Jason Chen
- Matt Gross
- Gisele Marguier
- Peter Shwonek
- Natalija Sotirovska
- Susanne Steggerda
- Francesco Parlati
- Amani Makkouk
- Mark K. Bennett
- Ethan Emberley
- Tony Huang
- Weiqun Li
- Silinda Neou
- Alison Pan
- Jing Zhang
- Winter Zhang
- Netonia Marshall
- Thomas U. Marron
- Judith Agudo
- Brian Brown
- Joshua Brody
- Christopher McQuinn
- Matthew Farren
- Hannah Komar
- Reena Shakya
- Thomas Ludwug
- Y. Maurice Morillon
- Scott A. Hammond
- Jeffrey Schlom
- John W. Greiner
- Pulak R. Nath
- Anthony L. Schwartz
- Dragan Maric
- David D. Roberts
- Aung Naing
- Kyriakos P. Papadopoulos
- Karen A. Autio
- Deborah J. Wong
- Manish Patel
- Gerald Falchook
- Shubham Pant
- Patrick A. Ott
- Melinda Whiteside
- Amita Patnaik
- John Mumm
- Filip Janku
- Ivan Chan
- Todd Bauer
- Rivka Colen
- Peter VanVlasselaer
- Gail L. Brown
- Nizar M. Tannir
- Martin Oft
- Jeffrey Infante
- Evan Lipson
- Ajay Gopal
- Sattva S. Neelapu
- Philippe Armand
- Stephen Spurgeon
- John P. Leonard
- F. Stephen Hodi
- Rachel E. Sanborn
- Ignacio Melero
- Thomas F. Gajewski
- Matthew Maurer
- Serena Perna
- Andres A. Gutierrez
- Raphael Clynes
- Priyam Mitra
- Satyendra Suryawanshi
- Douglas Gladstone
- Margaret K. Callahan
- James Crooks
- Sheila Brown
- Audrey Gauthier
- Marc Hillairet de Boisferon
- Andrew MacDonald
- Laura Rosa Brunet
- William T. Rothwell
- Peter Bell
- James M. Wilson
- Fumi Sato-Kaneko
- Shiyin Yao
- Shannon S. Zhang
- Dennis A. Carson
- Cristina Guiducci
- Robert L. Coffman
- Kazutaka Kitaura
- Takaji Matsutani
- Ryuji Suzuki
- Tomoko Hayashi
- Ezra E. W. Cohen
- David Schaer
- Yanxia Li
- Julie Dobkin
- Michael Amatulli
- Gerald Hall
- Thompson Doman
- Jason Manro
- Frank Charles Dorsey
- Lillian Sams
- Rikke Holmgaard
- Krishnadatt Persaud
- Dale Ludwig
- David Surguladze
- John S. Kauh
- Ruslan Novosiadly
- Michael Kalos
- Kyla Driscoll
- Hardev Pandha
- Christy Ralph
- Kevin Harrington
- Brendan Curti
- Rachel E. Sanborn
- Wallace Akerley
- Sumati Gupta
- Alan Melcher
- David Mansfield
- David R. Kaufman
- Emmett Schmidt
- Mark Grose
- Bronwyn Davies
- Roberta Karpathy
- Darren Shafren
- Katerina Shamalov
- Cyrille Cohen
- Naveen Sharma
- James Allison
- Tala Shekarian
- Sandrine Valsesia-Wittmann
- Christophe Caux
- Aurelien Marabelle
- Brian M. Slomovitz
- Kathleen M. Moore
- Hagop Youssoufian
- Marshall Posner
- Poonam Tewary
- Alan D. Brooks
- Ya-Ming Xu
- Kithsiri Wijeratne
- Leslie A. A. Gunatilaka
- Thomas J. Sayers
- John P. Vasilakos
- Tesha Alston
- Simon Dovedi
- James Elvecrog
- Iwen Grigsby
- Ronald Herbst
- Karen Johnson
- Craig Moeckly
- Stefanie Mullins
- Kristen Siebenaler
- Julius SternJohn
- Ashenafi Tilahun
- Mark A. Tomai
- Katharina Vogel
- Robert W. Wilkinson
- Eveline E. Vietsch
- Anton Wellstein
- Martin Wythes
- Stefano Crosignani
- Joseph Tumang
- Shilpa Alekar
- Patrick Bingham
- Sandra Cauwenberghs
- Jenny Chaplin
- Deepak Dalvie
- Sofie Denies
- Coraline De Maeseneire
- JunLi Feng
- Kim Frederix
- Samantha Greasley
- Jie Guo
- James Hardwick
- Stephen Kaiser
- Katti Jessen
- Erick Kindt
- Marie-Claire Letellier
- Wenlin Li
- Karen Maegley
- Reece Marillier
- Nichol Miller
- Brion Murray
- Romain Pirson
- Julie Preillon
- Virginie Rabolli
- Chad Ray
- Kevin Ryan
- Stephanie Scales
- Jay Srirangam
- Jim Solowiej
- Al Stewart
- Nicole Streiner
- Vince Torti
- Konstantinos Tsaparikos
- Xianxian Zheng
- Gregory Driessens
- Bruno Gomes
- Manfred Kraus
- Chunxiao Xu
- Yanping Zhang
- Giorgio Kradjian
- Guozhong Qin
- Jin Qi
- Xiaomei Xu
- Bo Marelli
- Huakui Yu
- Wilson Guzman
- Rober Tighe
- Rachel Salazar
- Kin-Ming Lo
- Jessie English
چکیده
4005. P299Phosphopeptides as novel tumor antigens in colorectal cancerSarah A Penny, Jennifer G Abelin, Abu Z Saeed, Stacy A Malaker,Paisley T Myers, Jeffrey Shabanowitz, Stephen T Ward, Donald FHunt, Mark CobboldUniversity of Birmingham, Birmingham, England, UK; University ofVirginia, Charlottesville, VA, USA; Stanford University, Stanford, CA, USA;Massachusetts General Hospital Cancer Center, Boston, MA, USACorrespondence: Sarah A Penny ([email protected])Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):P299 BackgroundThere is a pressing need for novel immunotherapeutic targets incolorectal cancer (CRC). Memory CD8+ T cell infiltration is now wellestablished as a key prognostic indicator in CRC, and it is known thatthese tumor infiltrating lymphocytes (TILs) are specifically targetingand killing tumor cells. However, the antigens that these TILs targethave not previously been determined. This has limited the use of immunotherapies in CRC, despite their efficacy in other cancer types.Recently, phosphopeptides have emerged as strong candidates fortumor-specific antigens, since dysregulation of signaling in cancersleads to aberrant protein phosphorylation. Here, we identify CRC-associated phosphopeptides and assess the tumor-resident immunityagainst these novel posttranslationally modified tumor antigens.Methods We compared tumor and healthy tissue from CRC patients, to iden-tify tumor-specific MHC class I associated phosphopeptides. Phos-phopeptides were enriched using immobilized metal affinitychromatography, and characterized using mass spectrometry. TILs,from the same tumors, were extracted and expanded, and their re-sponses to the phosphopeptides assessed using multiplexed intracellular cytokine staining. Cytolytic activity was observed by staining forsurface mobilization of CD107a. Healthy donor responses were quan-tified using interferon-γ ELISpot and functionality assessed using a europium release killing assay.ResultsWe have identified 133 tumor-associated MHC class I phosphopep-tides from CRC, with different HLA-restrictions. There were, on aver-age, 3.1 times more different phosphopeptides identified on primarycancers than healthy tissues, at 6.9-fold higher levels. 35 % of thesecan be attributed to signaling events in well-defined cancer path-ways and are therefore markers of malignancy. Through analysis ofTIL’s cytokine responses to these phosphopeptides, we have estab-lished that they are playing a key role in tumor-resident immunity.There were multifunctional TILs present in primary and metastatic tu-mors that recognized and killed in response to these phosphopep-tides. Up to 0.7 % of expanded TILs targeted each phosphopeptide,comparable with responses seen to viral epitopes. Immunity to thesetumor-associated phosphopeptides represents a biological strategyfor distinguishing tumor from healthy tissue. Furthermore, we haveshown that healthy donors have pre-existing, memory T cell re-sponses to many (58 %) of these CRC-associated phosphopeptides.These phosphopeptide-specific T cells are readily expanded ex vivoand kill CRC cell lines. Thus, MHC class I associated phosphopeptidesare ideal immunotherapeutic targets, as immunity must sparehealthy tissue.ConclusionsThe identification of this novel class of MHC class I antigens in CRCoffers new hope for the future of immunotherapy in this malignancy. P300Rapid and durable complete response to atezolizumab (anti-PD-L1), with sloughing of tumor tissue through urethra, in metastaticchemotherapy-resistant urothelial cancer (UC) Pam Profusek, Laura Wood, Dale Shepard, Petros Grivas Cleveland Clinic, Cleveland, OH, USACorrespondence: Pam Profusek ([email protected])Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):P300 BackgroundMetastatic UC is usually fatal causing significant morbidity. Atezo-lizumab, an anti-PD-L1 checkpoint inhibitor, is FDA-approved forlocally advanced or metastatic UC after progression on/afterplatinum-containing chemotherapy based on results of the IMvi-gor 210 trial.MethodsWe present a trial patient with unique sloughing of tumor tissue, out-standing treatment response and tolerance.ResultsA 76 year old man was diagnosed with high grade muscle-invasiveUC of the bladder in April 2013. Patient completed 3 cycles of ‘neo-adjuvant’ gemcitabine/cisplatin but had progression, he then re-ceived 6 cycles of docetaxel & investigational agent with progression,followed by 2 cycles of a targeted therapy on a phase I trial also withprogression. Patient was then screened for the cohort 2 of the IMVi-gor210 trial evaluating the use of atezolizumab, 1200 mg every21 days, in platinum-pretreated advanced UC. Screening CT showedthe bladder lumen replaced by multiple masses and a left peri-aorticnode 1.1 cm without other clear evidence of metastasis. Patient wasexperiencing fatigue, and hourly urgent urination with detrimentaleffect on his sleep, and overall quality of life (ECOG PS 1, normal GFR, Hgb 10.2 on Cycle 1 Day 1(C1D1). Tumor tissue analysis showedhigh PD-L1 expression in both tumor-infiltrating immune cells (IC2)and tumor cells (TC2), TCGA subtype IV (Basal), and a high mutationalload of 18.02 Mut/MB (compared to IMvigor210, Cohort 2 median of8.11 Mut/MB). At C2D1 visit, he already had major clinical benefitwith symptomatic improvement and sloughing of tumor tissue that passed through the urethra; the latter underwent pathology reviewand showed necrotic debris with highly atypical cells suspicious forcarcinoma. Ten days later he presented to the ED due to difficulty voiding; cystoscopy was performed to remove necrotic tissue passingthrough urethra. Scans at C3D1 demonstrated great response with83 % tumor reduction, he continued to have very good quality of life.Scans at C10D1 showed that the bladder mass was no longer meas-urable and the lymph node was stable. Patient continues on trialwithout notable adverse events (has asymptomatic atrial fibrillationthat was deemed possibly related to therapy) and has received 35 cycles. Patient remains very active, riding his bike most days of theweek, denies urinary issues, has ECOG PS 0, with durable completeresponse on scans. Journal for ImmunoTherapy of Cancer 2016, 4(Suppl 1):73Page 162 of 221 ConclusionsAtezolizumab can produce rapid and durable responses in advancedplatinum-resistant urothelial cancer and represents a new treatmentoption. Several clinical trials are ongoing.Trial RegistrationClinicalTrials.gov identifier NCT02108652. Fig. 40 (abstract P300). Bladder CT 9 Months of Therapy.
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عنوان ژورنال:
دوره 4 شماره
صفحات -
تاریخ انتشار 2016