JITC Digest May 2018

Letter from the Editor

Dear JITC Readers,

The Journal for ImmunoTherapy of Cancer (JITC) had yet another strong month in both submissions and visibility. I, along with other representatives from the journal, was pleased to meet and get to know many of JITC's authors and readers while attending recent conferences. JITC representatives will again travel to Chicago, Illinois this year for the American Society of Clinical Oncology (ASCO) Annual Meeting in June and hope to see you there at booth #3073.

Featured in this month's Clinical/Translational Cancer Immunotherapy section, Anandani Nellan et al. in "Durable regression of Medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells" evaluated the efficacy and safety of anti-HER2 - CD3zeta - 4-1BB CAR T cells (HER2-BBz) in pre-clinical medulloblastoma models. HER2-BBz cells effectively cleared tumors in mice bearing medulloblastoma through both tumor-directed and systemic delivery routes. Additionally, HER2-BBz cells were detected in brain tissues and blood samples from treated mice up to 30 days post-treatment. Finally, intraventricular delivery of HER2-BBz cells into non-human primates displayed increased IL-2 and IL-6 levels and no loss of neurological function. Together, these data demonstrate that HER2-BBz CAR T cells are both effective and safe in pre-clinical models, and offer potential for advancement into human trials.

Also of note, "Discovery and preclinical characterization of the antagonist anti-PD-L1 monoclonal antibody LY3300054," by Yiwen Li et al. is the first article to be published as part of JITC's 'Emerging Immunotherapeutic Agents' special series. Please be on the lookout for additional articles for this series in the coming month.

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

Recent Articles

Microsatellite instability in prostate cancer by PCR or next-generation sequencing

Jennifer A. Hempelmann, Christina M. Lockwood, Eric Q. Konnick, Michael T. Schweizer, Emmanuel S. Antonarakis, Tamara L. Lotan, Bruce Montgomery, Peter S. Nelson, Nola Klemfuss, Stephen J. Salipante and Colin C. Pritchard
Journal for ImmunoTherapy of Cancer, 6:29 (17 April 2018)
Research Article

From the Authors

"Microsatellite Instability (MSI) testing is beginning to be used to manage immunotherapy treatment decisions in patients with advanced prostate cancer. Our study shows that the most widely-used assay for detecting MSI has inferior sensitivity in prostate cancer compared to NGS-based methods that interrogate a larger number of microsatellite loci."

Colin C. Pritchard, PhD — University of Washington

An innovative immunotherapeutic strategy for ovarian cancer: CLEC10A and glycomimetic peptides

Laura L. Eggink, Katherine F. Roby, Robert Cote and J. Kenneth Hoober
Journal for ImmunoTherapy of Cancer, 6:28 (17 April 2018)
Research Article

From the Authors

"The potential for C-type (Ca2+-dependent) lectins (CLECs) as targets for immunotherapy rests on the expression of these receptors on cells at strategic points in the immune system and their ability to promote expansion of the innate and adaptive immune systems. To explore this approach, a tetravalent peptide was designed by Susavion Biosciences, Inc., that binds with high avidity to a C-type lectin receptor that is specific for N-acetylgalactosamine. Treatment of mice with small doses of the peptide promoted expansion of peritoneal immune cell populations and blocked accumulation of ascites in mice with implanted ovarian cancer cells. The peptide was effective as a monotherapy but also in combination with chemotherapeutic drugs or the antibody against the receptor PD-1. Our data show that the peptide induced maturation of immune cells in the peritoneal cavity and caused a highly significant extension of survival in this murine model of ovarian cancer with a favorable toxicity and non-antigenic profile."

J. Kenneth Hoober, PhD – Susavion Biosciences, Inc.

DISCOVERY AND PRECLINICAL CHARACTERIZATION OF THE ANTAGONIST ANTI-PD-L1 MONOCLONAL ANTIBODY LY3300054

Yiwen Li, Carmine Carpenito, George Wang, David Surguladze, Amelie Forest, Maria Malabunga, Mary Murphy, Yiwei Zhang, Andreas Sonyi, Darin Chin, Douglas Burtrum, Ivan Inigo, Anthony Pennello, Leyi Shen, Laurent Malherbe, Xinlei Chen, Gerald Hall, Jaafar N. Haidar, Dale L. Ludwig, Ruslan D. Novosiadly and Michael Kalos
Journal for ImmunoTherapy of Cancer, 6:31 (30 April 2018)
Research Article

From the Authors

"Immune therapies that target the PD-(L)1 axis have transformed the treatment landscape in oncology. In this report authors describe the preclinical development of a novel anti PD-L1 agent currently in clinical development, and use a series of immune- humanized mouse models to understand the activity and mechanism of action for this agent."

Michael Kalos, PhD — Janssen Oncology

Durable regression of Medulloblastoma after regional and intravenous delivery of anti-HER2 chimeric antigen receptor T cells*

Anandani Nellan†, Christopher Rota†, Robbie Majzner, Cynthia M. Lester-McCully, Andrea M. Griesinger, Jean M. Mulcahy Levy, Nicholas K. Foreman, Katherine E. Warren and Daniel W. Lee
Journal for ImmunoTherapy of Cancer, 6:30 (30 April 2018)
Research Article

From the Authors

"Effective treatments for relapsed medulloblastoma are lacking. Chimeric antigen receptor (CAR) T cell therapy holds great promise but also potential neurotoxicity due to a potential inflammatory immune response in the confines of the central nervous system. This pre-clinical study demonstrates that a small intracranial dose of a new HER2-targeted CAR T cell therapy is effective against xenografts with stereotactically implanted medulloblastoma. Further, CAR T cells administered and activated within the CSF of non-human primates did not induce toxicity."

Daniel W. Lee, MD — University of Virginia

*This article is part of JITC’s Emerging Immunotherapeutic Agents special series. All articles in this series cover details beyond standard JITC articles, providing readers with a unique collection of cutting-edge cancer immunotherapy research.

Highly Accessed Articles

Efficacy of PD-1 & PD-L1 inhibitors in older adults: a meta-analysis

Rawad Elias, Anita Giobbie-Hurder, Nadine Jackson McCleary, Patrick Ott, F. Stephen Hodi and Osama Rahma
Journal for ImmunoTherapy of Cancer 2018, 6:26 (4 April 2018)

Coordinated responses to individual tumor antigens by IgG antibody and CD8+ T cells following cancer vaccination

Tyler W. Hulett, Shawn M. Jensen, Phillip A. Wilmarth, Ashok P. Reddy, Carmen Ballesteros-Merino, Michael E. Afentoulis, Christopher Dubay, Larry L. David and Bernard A. Fox
Journal for ImmunoTherapy of Cancer 2018, 6:27 (5 April 2018)

Submit Your Research to JITC

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• Hypothesis
• Meeting report
• Position article and guidelines
• Research article
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JITC Editor-in-Chief

Pedro J. Romero, MD – University of Lausanne

Section Editors

• Basic Tumor Immunology: Cornelis J.M. Melief, MD, PhD – ISA Therapeutics BV
• Case Reports: Alfred Zippelius, MD – University Hospital Basel
• Clinical/Translational Cancer Immunology: James L. Gulley, MD, PhD, FACP – National Cancer Institute, National Institutes of Health
• Clinical Trials Monitor: Leisha A. Emens, MD, PhD – Johns Hopkins University
• Commentary/Editorials: Christian Capitini, MD – University of Wisconsin - Madison
• Guidelines and Consensus Statements: Robert L. Ferris, MD, PhD – University of Pittsburgh Cancer Institute
• Immunotherapy Biomarkers: Lisa H. Butterfield, PhD – University of Pittsburgh Cancer Institute
• Reviews: Sandra Demaria, MD – Weill Cornell Medical College; Thomas F. Gajewski, MD, PhD – University of Chicago

To view the full editorial board, please click here.

*As a way to thank the dedicated society members who tirelessly work to advance the science and ultimately to improve the lives of patients with cancer, one article per SITC member is eligible for waived article processing charges through 2018. To take advantage of this benefit valued at more than $2,400, authors must contact JITC Managing Editor Andrea Rindo at JITCEditor@sitcancer.org or 1-414-271-2456 prior to submission to obtain a discount code and instructions.

 Become a Member!

Journal for ImmunoTherapy of Cancer (JITC) is the official, online, open access journal of the Society for Immunotherapy of Cancer (SITC) and considered BMC’s premier cancer immunotherapy journal. JITC welcomes basic, translational and clinical research and literature reviews on any aspect of tumor immunology and cancer immunotherapy. Topics of interest include tumor-host interactions, immune biomarkers, novel therapeutics, and immune-related toxicity.  The journal’s full collection, including its seminal guidelines and consensus statements, advances the rapidly evolving field of cancer immunotherapy through dissemination of rigorous peer-reviewed research.