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jedd wolchok

Dmitriy Zamarin, Jacob M Ricca, Svetlana Sadekova, Anton Oseledchyk, Ying Yu, Wendy M Blumenschein, Jerelyn Wong, Mathieu Gigoux, Taha Merghoub, Jedd D Wolchok
Intralesional therapy with oncolytic viruses (OVs) leads to the activation of local and systemic immune pathways, which may present targets for further combinatorial therapies. Here, we used human tumor histocultures as well as syngeneic tumor models treated with Newcastle disease virus (NDV) to identify a range of immune targets upregulated with OV treatment. Despite tumor infiltration of effector T lymphocytes in response to NDV, there was ongoing inhibition through programmed death ligand 1 (PD-L1), acting as a mechanism of early and late adaptive immune resistance to the type I IFN response and T cell infiltration, respectively...
March 5, 2018: Journal of Clinical Investigation
Min Yuen Teo, Kenneth Seier, Irina Ostrovnaya, Ashley M Regazzi, Brooke E Kania, Meredith M Moran, Catharine K Cipolla, Mark J Bluth, Joshua Chaim, Hikmat Al-Ahmadie, Alexandra Snyder, Maria I Carlo, David B Solit, Michael F Berger, Samuel Funt, Jedd D Wolchok, Gopa Iyer, Dean F Bajorin, Margaret K Callahan, Jonathan E Rosenberg
Purpose Alterations in DNA damage response and repair (DDR) genes are associated with increased mutation load and improved clinical outcomes in platinum-treated metastatic urothelial carcinoma. We examined the relationship between DDR alterations and response to PD-1/PD-L1 blockade. Methods Detailed demographic, treatment response, and long-term outcome data were collected on patients with metastatic urothelial carcinoma treated with atezolizumab or nivolumab who had targeted exon sequencing performed on pre-immunotherapy tumor specimens...
February 28, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Jacob M Ricca, Anton Oseledchyk, Tyler Walther, Cailian Liu, Levi Mangarin, Taha Merghoub, Jedd D Wolchok, Dmitriy Zamarin
Anti-viral immunity presents a major hurdle for systemically administered oncolytic viruses (OV). Intratumoral OV therapy has a potential to overcome this problem through activation of anti-tumor immune response, with local and abscopal effects. However, the effects of anti-viral immunity in such a setting are still not well defined. Using Newcastle Disease Virus (NDV) as a model, we explore the effects of pre-existing anti-viral immunity on therapeutic efficacy in syngeneic mouse tumor models. Unexpectedly, we find that while pre-existing immunity to NDV limits its replication in tumors, tumor clearance, abscopal anti-tumor immune effects, and survival are not compromised and, on the contrary, are superior in NDV-immunized mice...
January 31, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Ignacio Melero, Mario Sznol, Marlowe S Tessmer, Theresa L Whiteside, Jedd D Wolchok
No abstract text is available yet for this article.
February 23, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Samuel Rosner, Erica Kwong, Alexander N Shoushtari, Claire F Friedman, Allison S Betof, Mary Sue Brady, Daniel G Coit, Margaret K Callahan, Jedd D Wolchok, Paul B Chapman, Katherine S Panageas, Michael A Postow
Both the combination of nivolumab + ipilimumab and single-agent anti-PD-1 immunotherapy have demonstrated survival benefit for patients with advanced melanoma. As the combination has a high rate of serious side effects, further analyses in randomized trials of combination versus anti-PD-1 immunotherapy are needed to understand who benefits most from the combination. Clinical laboratory values that were routinely collected in randomized studies may provide information on the relative benefit of combination immunotherapy...
February 22, 2018: Cancer Medicine
Julie R Brahmer, Christina Lacchetti, Bryan J Schneider, Michael B Atkins, Kelly J Brassil, Jeffrey M Caterino, Ian Chau, Marc S Ernstoff, Jennifer M Gardner, Pamela Ginex, Sigrun Hallmeyer, Jennifer Holter Chakrabarty, Natasha B Leighl, Jennifer S Mammen, David F McDermott, Aung Naing, Loretta J Nastoupil, Tanyanika Phillips, Laura D Porter, Igor Puzanov, Cristina A Reichner, Bianca D Santomasso, Carole Seigel, Alexander Spira, Maria E Suarez-Almazor, Yinghong Wang, Jeffrey S Weber, Jedd D Wolchok, John A Thompson
Purpose To increase awareness, outline strategies, and offer guidance on the recommended management of immune-related adverse events in patients treated with immune checkpoint inhibitor (ICPi) therapy. Methods A multidisciplinary, multi-organizational panel of experts in medical oncology, dermatology, gastroenterology, rheumatology, pulmonology, endocrinology, urology, neurology, hematology, emergency medicine, nursing, trialist, and advocacy was convened to develop the clinical practice guideline. Guideline development involved a systematic review of the literature and an informal consensus process...
February 14, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Jedd D Wolchok
No abstract text is available yet for this article.
February 5, 2018: Nature Reviews. Immunology
Jedd D Wolchok, Margaret K Callahan
No abstract text is available yet for this article.
January 2018: Cancer Journal
Madhav D Sharma, Paulo C Rodriguez, Brent H Koehn, Babak Baban, Yan Cui, Gang Guo, Michiko Shimoda, Rafal Pacholczyk, Huidong Shi, Eun-Joon Lee, Hongyan Xu, Theodore S Johnson, Yukai He, Taha Mergoub, Christopher Venable, Vincenzo Bronte, Jedd D Wolchok, Bruce R Blazar, David H Munn
CD103+ dendritic cells are critical for cross-presentation of tumor antigens. Here we have shown that during immunotherapy, large numbers of cells expressing CD103 arose in murine tumors via direct differentiation of Ly6c+ monocytic precursors. These Ly6c+ CD103+ cells could derive from bone-marrow monocytic progenitors (cMoPs) or from peripheral cells present within the myeloid-derived suppressor cell (MDSC) population. Differentiation was controlled by inflammation-induced activation of the transcription factor p53, which drove upregulation of Batf3 and acquisition of the Ly6c+ CD103+ phenotype...
January 16, 2018: Immunity
F Stephen Hodi, Marcus Ballinger, Benjamin Lyons, Jean-Charles Soria, Mizuki Nishino, Josep Tabernero, Thomas Powles, David Smith, Axel Hoos, Chris McKenna, Ulrich Beyer, Ina Rhee, Gregg Fine, Nathan Winslow, Daniel S Chen, Jedd D Wolchok
Purpose Treating solid tumors with cancer immunotherapy (CIT) can result in unconventional responses and overall survival (OS) benefits that are not adequately captured by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. We describe immune-modified RECIST (imRECIST) criteria, designed to better capture CIT responses. Patients and Methods Atezolizumab data from clinical trials in non-small-cell lung cancer, metastatic urothelial carcinoma, renal cell carcinoma, and melanoma were evaluated. Modifications to imRECIST versus RECIST v1...
March 20, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
Hira Rizvi, Francisco Sanchez-Vega, Konnor La, Walid Chatila, Philip Jonsson, Darragh Halpenny, Andrew Plodkowski, Niamh Long, Jennifer L Sauter, Natasha Rekhtman, Travis Hollmann, Kurt A Schalper, Justin F Gainor, Ronglai Shen, Ai Ni, Kathryn C Arbour, Taha Merghoub, Jedd Wolchok, Alexandra Snyder, Jamie E Chaft, Mark G Kris, Charles M Rudin, Nicholas D Socci, Michael F Berger, Barry S Taylor, Ahmet Zehir, David B Solit, Maria E Arcila, Marc Ladanyi, Gregory J Riely, Nikolaus Schultz, Matthew D Hellmann
Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240)...
March 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Parisa Momtaz, James J Harding, Charlotte Ariyan, Daniel G Coit, Taha Merghoub, Billel Gasmi, Daoqi You, Agnes Viale, Katherine S Panageas, Aliaksandra Samoila, Michael A Postow, Jedd D Wolchok, Paul B Chapman
Background: We tested the hypothesis that a 4-month course of adjuvant dabrafenib in stage IIIC BRAF-mutated melanoma would improve 2 year RFS from 24% to 51%, and that tumor-derived cell free DNA (cfDNA) in plasma would correlate with and predict recurrence. Methods: Patients with stage IIIC BRAF V600E/K mutated melanoma who were free of disease after surgical resection received 4 months of adjuvant dabrafenib. Patients were evaluated with imaging at baseline, at the end of cycles 2, 4, 6, then every 3 months until disease relapse or 2 years, whichever came first...
December 1, 2017: Oncotarget
Caroline Robert, Antoni Ribas, Omid Hamid, Adil Daud, Jedd D Wolchok, Anthony M Joshua, Wen-Jen Hwu, Jeffrey S Weber, Tara C Gangadhar, Richard W Joseph, Roxana Dronca, Amita Patnaik, Hassane Zarour, Richard Kefford, Peter Hersey, Jin Zhang, James Anderson, Scott J Diede, Scot Ebbinghaus, F Stephen Hodi
Purpose Pembrolizumab provides durable antitumor activity in metastatic melanoma, including complete response (CR) in about 15% of patients. Data are limited on potential predictors of CR and patient disposition after pembrolizumab discontinuation after CR. We describe baseline characteristics and long-term follow-up in patients who experienced CR with pembrolizumab in the KEYNOTE-001 study ( identifier: NCT01295827). Patients and Methods Patients with ipilimumab-naive or -treated advanced/metastatic melanoma received one of three dose regimens of pembrolizumab...
December 28, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Elizabeth M Jaffee, Chi Van Dang, David B Agus, Brian M Alexander, Kenneth C Anderson, Alan Ashworth, Anna D Barker, Roshan Bastani, Sangeeta Bhatia, Jeffrey A Bluestone, Otis Brawley, Atul J Butte, Daniel G Coit, Nancy E Davidson, Mark Davis, Ronald A DePinho, Robert B Diasio, Giulio Draetta, A Lindsay Frazier, Andrew Futreal, Sam S Gambhir, Patricia A Ganz, Levi Garraway, Stanton Gerson, Sumit Gupta, James Heath, Ruth I Hoffman, Cliff Hudis, Chanita Hughes-Halbert, Ramy Ibrahim, Hossein Jadvar, Brian Kavanagh, Rick Kittles, Quynh-Thu Le, Scott M Lippman, David Mankoff, Elaine R Mardis, Deborah K Mayer, Kelly McMasters, Neal J Meropol, Beverly Mitchell, Peter Naredi, Dean Ornish, Timothy M Pawlik, Jeffrey Peppercorn, Martin G Pomper, Derek Raghavan, Christine Ritchie, Sally W Schwarz, Richard Sullivan, Richard Wahl, Jedd D Wolchok, Sandra L Wong, Alfred Yung
We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment...
November 2017: Lancet Oncology
Vinod P Balachandran, Marta Łuksza, Julia N Zhao, Vladimir Makarov, John Alec Moral, Romain Remark, Brian Herbst, Gokce Askan, Umesh Bhanot, Yasin Senbabaoglu, Daniel K Wells, Charles Ian Ormsby Cary, Olivera Grbovic-Huezo, Marc Attiyeh, Benjamin Medina, Jennifer Zhang, Jennifer Loo, Joseph Saglimbeni, Mohsen Abu-Akeel, Roberta Zappasodi, Nadeem Riaz, Martin Smoragiewicz, Z Larkin Kelley, Olca Basturk, Mithat Gönen, Arnold J Levine, Peter J Allen, Douglas T Fearon, Miriam Merad, Sacha Gnjatic, Christine A Iacobuzio-Donahue, Jedd D Wolchok, Ronald P DeMatteo, Timothy A Chan, Benjamin D Greenbaum, Taha Merghoub, Steven D Leach
Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival...
November 23, 2017: Nature
Marta Łuksza, Nadeem Riaz, Vladimir Makarov, Vinod P Balachandran, Matthew D Hellmann, Alexander Solovyov, Naiyer A Rizvi, Taha Merghoub, Arnold J Levine, Timothy A Chan, Jedd D Wolchok, Benjamin D Greenbaum
Checkpoint blockade immunotherapies enable the host immune system to recognize and destroy tumour cells. Their clinical activity has been correlated with activated T-cell recognition of neoantigens, which are tumour-specific, mutated peptides presented on the surface of cancer cells. Here we present a fitness model for tumours based on immune interactions of neoantigens that predicts response to immunotherapy. Two main factors determine neoantigen fitness: the likelihood of neoantigen presentation by the major histocompatibility complex (MHC) and subsequent recognition by T cells...
November 23, 2017: Nature
Cindy L Zuleger, Chulhi Kang, Erik A Ranheim, Ilene D Kurzman, Michael D Macklin, Michael A Newton, Jedd D Wolchok, David M Vail, Elof Eriksson, Mark R Albertini
Spontaneous canine malignant melanoma provides an excellent pre-clinical model to study DNA vaccines for melanoma immunotherapy. A USDA-approved xenogeneic human tyrosinase (huTYR) plasmid DNA vaccine delivered intramuscularly induces detectable immune responses and has clinical activity in some dogs with melanoma. The objective of this pilot study was to evaluate the feasibility, safety and immunogenicity of huTYR plasmid DNA administered to the skin via microseeding in dogs with spontaneous melanoma. DNA microseeding utilizes a modified tattooing device as an alternate and potentially more potent delivery method for DNA immunization...
August 2017: Veterinary Medicine and Science
Margaret K Callahan, Harriet Kluger, Michael A Postow, Neil H Segal, Alexander Lesokhin, Michael B Atkins, John M Kirkwood, Suba Krishnan, Rafia Bhore, Christine Horak, Jedd D Wolchok, Mario Sznol
Purpose The clinical activity observed in a phase I dose-escalation study of concurrent therapy with nivolumab (NIVO) and ipilimumab (IPI) in patients with previously treated or untreated advanced melanoma led to subsequent clinical development, including randomized trials. Here, we report long-term follow-up data from study CA209-004, including 3-year overall survival (OS). Patients and Methods Concurrent cohorts 1, 2, 2a, and 3 received escalating doses of NIVO plus IPI once every 3 weeks for four doses, followed by NIVO once every 3 weeks for four doses, then NIVO plus IPI once every 12 weeks for eight doses...
February 1, 2018: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
Erik S Anderson, Michael A Postow, Jedd D Wolchok, Robert J Young, Åse Ballangrud, Timothy A Chan, Yoshiya Yamada, Kathryn Beal
BACKGROUND: Brain metastases are common in patients with metastatic melanoma. With increasing numbers of melanoma patients on anti-PD-1 therapy, we sought to evaluate the safety and initial response of brain metastases treated with concurrent pembrolizumab and radiation therapy. METHODS: From an institutional database, we retrospectively identified patients with melanoma brain metastases treated with radiation therapy (RT) who received concurrent pembrolizumab. Concurrent treatment was defined as RT during pembrolizumab administration period and up to 4 months after most recent pembrolizumab treatment...
October 17, 2017: Journal for Immunotherapy of Cancer
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