JITC Digest September 2017


Inside this Issue:

Letter from the Editor

pedro-romero_1__1_.jpgDear JITC Readers:

As we welcome a new season, I am pleased to feature in this issue of the Journal for ImmunoTherapy of Cancer (JITC), a report from SITC’s one-day ‘Workshop on Challenges, Insights, and Future Directions for Mouse and Humanized Models in Cancer Immunology and Immunotherapy’. The report from this workshop, which was held in conjunction with SITC’s 31st Annual Meeting in 2016, provides an introduction to immunocompetent and humanized models commonly used in cancer immunology and immunotherapy research, and addresses ways to improve the predictive value of mouse models. Most usefully, it also covers anticipated advances in cancer modeling.

Also featured in this issue, “Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC”, by Caroline Tosch et al., aims to elucidate the mechanisms behind the increased overall survival (OS) observed following administration of TG4010, a recombinant viral vaccine encoding for human mucin 1 (MUC1) and interleukin-2 (IL-2), in patients with advanced non-small cell lung cancer (NSCLC). Researchers sought to establish an association between overall survival (OS) in vaccine-treated patients and vaccine-induced T cell responses against tumor associated antigens (TAA). Based on a study of 78 patients carrying the HLA-A02*01 haplotype in the TIME study, it was determined that OS in patients treated with TG4010 correlated with development of T cell responses against MUC1. Responses against MUC1 led to a broad CD8 T cell response against non-targeted TAA, providing evidence of epitope spreading. The results suggest that TG4010 may improve response rate and increase clinical benefit in association with other targeted immuno-modulators. This is the first report to date linking the development of a specific immune response to the success of a viral-based vaccine in patients with advanced NSCLC. The findings may open new avenues for similar treatments against other types of cancer.

With best regards,
Pedro J. Romero, MD
Editor-in-Chief, Journal for ImmunoTherapy of Cancer

Case Report

Checkpoint inhibitor is active against large cell neuroendocrine carcinoma with high tumor mutation burden

Victoria E. Wang, Anatoly Urisman, Lee Albacker, Siraj Ali, Vincent Miller, Rahul Aggarwal and David Jablons
Journal for ImmunoTherapy of Cancer 2017, 5:75 (19 September 2017)

From the Authors

"Our article highlights the robust and durable response of a case of large cell neuroendocrine carcinoma, a rare and aggressive tumor, to checkpoint inhibitor therapy."

Victoria Wang, MD, PhD — University of California, San Francisco

Meeting Report

Workshop on challenges, insights, and future directions for mouse and humanized models in cancer immunology and immunotherapy: a report from the associated programs of the 2016 annual meeting for the Society for Immunotherapy of cancer

Andrew Zloza, A. Karolina Palucka, Lisa M. Coussens, Philip J. Gotwals, Mark B. Headley, Elizabeth M. Jaffee, Amanda W. Lund, Arlene H. Sharpe, Mario Sznol, Derek A. Wainwright, Kwok-Kin Wong and Marcus W. Bosenberg
Journal for ImmunoTherapy of Cancer 2017, 5:77 (19 September 2017)

From the Authors

"With a rapidly increasing number of newly discovered immune and cancer cell pathways and mediators, models for unraveling basic mechanisms and vetting potential drugs are needed. Thus, we held this workshop to discuss in an open forum the advantages and disadvantages of current models and to highlight future needs. The result was a shared appreciation of the vital tools with which current models (including transplantable tumor, genetically engineered, and humanized mouse) provide the field of cancer immunology and immunotherapy. A resounding call was made for further innovation in modeling to meet the demands of testing combinatorial cancer therapies, understanding the tumor microenvironment, predicting outcomes and toxicity, and utilizing cancer patient-derived tissues for impactful translation from pre-clinical observation to clinical cure."

Andrew Zloza, MD, PhD — Rutgers Cancer Institute of New Jersey

Research Articles

Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma

Veronika Kremer, Maarten Ligtenberg, Rosa Zendehdel, Christina Seitz, Annet Duivenvoorden, Erik Wennerberg, Eugenia Colón, Ann-Helén Scherman-Plogell and Andreas Lundqvist
Journal for ImmunoTherapy of Cancer 2017, 5:73 (19 September 2017)

From the Authors

"Clinical responses of NK cell-based therapies in patients with solid tumors are potentially limited by ineffective homing of the infused NK cells to the tumor site. Here we show that genetic modification of human primary NK cells to re-express the chemokine receptor CXCR2 is a promising strategy to enhance their migration to recombinant CXCR2 ligands and RCC tumor supernatants and thereby improve anti-tumor responses."

Andreas Lundqvist, PhD — Karolinska Institutet

Durable response rate as an endpoint in cancer immunotherapy: insights from oncolytic virus clinical trials

Howard L. Kaufman, Robert H. I. Andtbacka, Frances A. Collichio, Michael Wolf, Zhongyun Zhao, Mark Shilkrut, Igor Puzanov and Merrick Ross
Journal for ImmunoTherapy of Cancer 2017, 5:72 (19 September 2017)

From the Authors

"Finding appropriate clinical study endpoints that incorporate the true potential of immunotherapy agents is a high priority for the field. In this paper, we show that durable response rate, as used in an oncolytic virus immunotherapy study, was validated as such an endpoint with a positive association with other more standard endpoints. Clinical investigators should consider durable response rate as a clinically meaningful endpoint for clinical protocol development with immunotherapy agents and regimens."

Howard L. Kaufman, MD, FACS — Rutgers Cancer Institute of New Jersey

Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection

Rocio Garcia-Carbonero, Ramon Salazar, Ignacio Duran, Ignacio Osman-Garcia, Luis Paz-Ares, Juan M. Bozada, Valentina Boni, Christine Blanc, Len Seymour, John Beadle, Simon Alvis, Brian Champion, Emiliano Calvo and Kerry Fisher
Journal for ImmunoTherapy of Cancer 2017, 5:71 (19 September 2017)

From the Authors

"This phase I study demonstrates for the first time that a group B oncolytic adenovirus can be injected intravenously, survive within the blood stream and then be found replicating extensively in tumor cells. The study is important because it paves the way for using oncolytic virotherapy, including therapeutic transgene-bearing viruses, to treat disseminated disease, avoiding the need for direct injection of each tumor deposit."

Brian R. Champion, PhD — PsiOxus Therapeutics Ltd.

Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC

Caroline Tosch, Bérangère Bastien, Luc Barraud, Benoit Grellier, Virginie Nourtier, Murielle Gantzer, Jean Marc Limacher, Eric Quemeneur, Kaïdre Bendjama and Xavier Préville
Journal for ImmunoTherapy of Cancer 2017, 5:70 (19 September 2017)

From the Authors

"Retrospective analysis of samples from the TIME trial, a phase 2 trial evaluating the MUC1-targeted viral based cancer vaccine TG4010 in NSCLC, shows an association between development of specific cell-mediated immune response and patient outcome. Administration of TG4010 correlated with the development of a specific T cell response against MUC1 and with a broadening of the immune repertoire against other tumor-associated antigens leading to extended patient survival."

Kaïdre Bendjama — Transgene

High-dose interleukin-2 (HD IL-2) for advanced melanoma: a single center experience from the University of Pittsburgh Cancer Institute

Diwakar Davar, Fei Ding, Melissa Saul, Cindy Sander, Ahmad A. Tarhini, John M. Kirkwood and Hussein A. Tawbi
Journal for ImmunoTherapy of Cancer 2017, 5:74 (19 September 2017)

From the Authors

"Prior to the advent of PD-1 inhibitors, HD IL-2 and adoptive cellular therapies were the most effective means of treating advanced melanoma. While the arrival of PD-1 inhibitors and combinations have transformed the landscape of advanced melanoma, this report of 273 patients from the University of Pittsburgh treated in the modern era identifies some new prognostic factors; and suggests that HD IL-2 may retain a role in the melanoma treatment armamentarium."

Diwikar Davar, MD — University of Pittsburgh Cancer Institute

August Highly Accessed Articles


Response to single agent PD-1 inhibitor after progression on previous PD-1/PD-L1 inhibitors: a case series

Dylan J. Martini, Aly-Khan A. Lalani, Dominick Bossé, John A. Steinharter, Lauren C. Harshman, F. Stephen Hodi, Patrick A. Ott and Toni K. Choueiri
Journal for ImmunoTherapy of Cancer 2017, 5:66 (15 August 2017)


Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of bladder carcinoma

Ashish M. Kamat, Joaquim Bellmunt, Matthew D. Galsky, Badrinath R. Konety, Donald L. Lamm, David Langham, Cheryl T. Lee, Matthew I. Milowsky, Michael A. O’Donnell, Peter H. O’Donnell, Daniel P. Petrylak, Padmanee Sharma, Eila C. Skinner, Guru Sonpavde, John A. Taylor III, Prasanth Abraham and Jonathan E. Rosenberg
Journal for ImmunoTherapy of Cancer 2017, 5:68 (15 August 2017)