Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer.
Dung T. Le,Eric R. Lutz,Jennifer N. Uram,Elizabeth A. Sugar,Beth Onners,Sara Solt,Lei Zheng,Luis A. Diaz,Ross C. Donehower,Elizabeth M. Jaffee,Daniel A. Laheru +10 more
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TLDR
Ipilimumab (anti-CTLA-4) has been tested as a single agent in patients with pancreatic ductal adenocarcinoma and in combination with GVAX has the potential for clinical benefit and should be evaluated in a larger study.Abstract:
Preclinical reports support the concept of synergy between cancer vaccines and immune checkpoint blockade in nonimmunogenic tumors. In particular, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibodies have been successfully combined with GM-CSF cell-based vaccines (GVAX). Ipilimumab (anti-read more
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The future of immune checkpoint therapy
Padmanee Sharma,James P. Allison +1 more
TL;DR: The way forward for this class of novel agents lies in the ability to understand human immune responses in the tumor microenvironment, which will provide valuable information regarding the dynamic nature of the immune response and regulation of additional pathways that will need to be targeted through combination therapies to provide survival benefit for greater numbers of patients.
Journal ArticleDOI
Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy.
TL;DR: As the molecular mechanisms of resistance to immunotherapy are elucidated, actionable strategies to prevent or treat them may be derived to improve clinical outcomes for patients.
Journal ArticleDOI
Immune Checkpoint Blockade in Cancer Therapy
TL;DR: Concluding remarks are made that principles learned during the development of CTLA-4 and PD-1/PD-L1 approaches will likely be used as new immunologic checkpoint blocking antibodies begin clinical investigation, and whether they enhance the efficacy of either approach alone is investigated.
Journal ArticleDOI
CSF1/CSF1R Blockade Reprograms Tumor-Infiltrating Macrophages and Improves Response to T-cell Checkpoint Immunotherapy in Pancreatic Cancer Models
Yu Zhu,Brett L. Knolhoff,Melissa A. Meyer,Timothy M. Nywening,Brian L. West,Jingqin Luo,Andrea Wang-Gillam,S. Peter Goedegebuure,David C. Linehan,David G. DeNardo +9 more
TL;DR: It is demonstrated in a mouse model of pancreatic ductal adenocarcinoma (PDAC) that inhibiting signaling by the myeloid growth factor receptor CSF1R can functionally reprogram macrophage responses that enhance antigen presentation and productive antitumor T-cell responses.
Journal ArticleDOI
Immune Escape Mechanisms as a Guide for Cancer Immunotherapy
TL;DR: This work discusses immune escape mechanisms exploited by cancer and presents strategies for applying this knowledge to improving the efficacy of cancer immunotherapy.
References
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Journal ArticleDOI
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma.
F. Stephen Hodi,Steven J. O'Day,David F. McDermott,R. W. Weber,Jeffrey A. Sosman,John B. A. G. Haanen,Rene Gonzalez,Caroline Robert,Dirk Schadendorf,Jessica C. Hassel,Wallace Akerley,Alfons J.M. van den Eertwegh,Jose Lutzky,Paul Lorigan,Julia Vaubel,Gerald P. Linette,David W. Hogg,Christian H. Ottensmeier,Céleste Lebbé,Christian Peschel,Ian Quirt,Joseph I. Clark,Jedd D. Wolchok,Jeffrey S. Weber,Jason Tian,Michael Yellin,Geoffrey M. Nichol,Axel Hoos,Walter J. Urba +28 more
TL;DR: Ipilimumab, with or without a gp100 peptide vaccine, as compared with gp100 alone, improved overall survival in patients with previously treated metastatic melanoma.
Journal ArticleDOI
Safety, activity, and immune correlates of anti-PD-1 antibody in cancer.
Suzanne L. Topalian,F. Stephen Hodi,Julie R. Brahmer,Scott N. Gettinger,David Smith,David F. McDermott,John D. Powderly,Richard D. Carvajal,Jeffrey A. Sosman,Michael B. Atkins,Philip D. Leming,David R. Spigel,Scott J. Antonia,Leora Horn,Charles G. Drake,Drew M. Pardoll,Lieping Chen,William H. Sharfman,Robert A. Anders,Janis M. Taube,Tracee L. McMiller,Haiying Xu,Alan J. Korman,Maria Jure-Kunkel,Shruti Agrawal,Dan McDonald,Georgia Kollia,Ashok Kumar Gupta,Jon M. Wigginton,Mario Sznol +29 more
TL;DR: Anti-PD-1 antibody produced objective responses in approximately one in four to one in five patients with non-small-cell lung cancer, melanoma, or renal-cell cancer; the adverse-event profile does not appear to preclude its use.
Journal ArticleDOI
Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer
Julie R. Brahmer,Scott S. Tykodi,Scott S. Tykodi,Laura Q.M. Chow,Wen-Jen Hwu,Suzanne L. Topalian,Patrick Hwu,Charles G. Drake,Luis H. Camacho,John S. Kauh,Kunle Odunsi,Henry C. Pitot,Omid Hamid,Shailender Bhatia,Renato G. Martins,Keith D. Eaton,Shuming Chen,Theresa M. Salay,Suresh Alaparthy,Joseph F. Grosso,Alan J. Korman,Susan M. Parker,Shruti Agrawal,Stacie M. Goldberg,Drew M. Pardoll,Ashok Kumar Gupta,Jon M. Wigginton +26 more
TL;DR: Antibody-mediated blockade of PD-L1 induced durable tumor regression and prolonged stabilization of disease in patients with advanced cancers, including non-small-cell lung cancer, melanoma, and renal-cell cancer.
Journal ArticleDOI
FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer
Thierry Conroy,Françoise Desseigne,Marc Ychou,Olivier Bouché,Rosine Guimbaud,Yves Becouarn,Antoine Adenis,Jean-Luc Raoul,Sophie Gourgou-Bourgade,Jaafar Bennouna,Jean-Baptiste Bachet,Faiza Khemissa-Akouz,Denis Péré-Vergé,Catherine Delbaldo,Eric Assenat,Bruno Chauffert,C. Montoto-Grillot,Michel Ducreux +17 more
TL;DR: FOLFIRINOX was associated with a survival advantage and had increased toxicity as compared with gemcitabine, and is an option for the treatment of patients with metastatic pancreatic cancer and good performance status.
Journal ArticleDOI
Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
Philip W. Kantoff,Celestia S. Higano,N. Shore,E. Roy Berger,Eric J. Small,David F. Penson,Charles H. Redfern,Anna C. Ferrari,Robert Dreicer,Robert B. Sims,Yi Xu,Mark W. Frohlich,Paul F. Schellhammer +12 more
TL;DR: The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer and immune responses to the immunizing antigen were observed in patients who received sipuleUcel- T.
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