JITC Digest – March 2016

Letter from the Editor

Dear JITC Readers:

Cancer immunotherapy is increasingly offering many unsuspected and unique properties and opportunities. As a result, the rigorous testing of novel immunotherapeutic treatments is showing promising alternatives to, as well as rationales for combinations with, other conventional therapeutic approaches. This month’s issue of JITC includes two outstanding articles related to various aspects of immunotherapeutic clinical trials.

The research article entitled “Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study,” by Howard Kaufman and colleagues, describes the elucidation of the local versus systematic responses in melanoma patients treated with an oncolytic virus approved by the FDA in 2015 for the treatment of advanced melanoma patients with accessible metastasis.

The review article by Holbrook Kohrt and colleagues entitled “IMMUNODYNAMICS: A Cancer Immunotherapy Trials Network Review of Immune Monitoring in Immuno-Oncology Clinical Trials,” describes the work of the Cancer Immunotherapy Trials Network investigators, with whom SITC has had a wonderful working relationship since its inception. By extension of the term pharmacodynamics to the tracking of variation in defined immune parameters upon therapy, the authors introduce the term “immunodynamic” effects for those that are associated with specific classes of immunotherapeutic agents. They focus on reviewing immune assessment modalities and sites, both systemic and intratumoral, which are critical to the success of the rapidly growing field of immuno-oncology. As you may know, Dr. Kohrt sadly passed away on February 24, 2016, at the young age of 38. Having used his own chronic condition of hemophilia as a conduit to a career dedicated to finding medical cures, Dr. Kohrt was a tireless champion of SITC and its important work. Dr. Kohrt was one of the organizers for the 2016 SITC Annual Meeting and a tribute to him will take place at the meeting.

Best regards,

Pedro J. Romero, MD
Editor in Chief, Journal for ImmunoTherapy of Cancer (JITC)

JITC Now Discoverable in 5 Major Indexing Databases!

In addition to being indexed in PubMed, PubMed Central, the Directory of Open Access Journals (DOAJ),and Thomson Reuters’ Emerging Sources Citation Index (ESCI), we are pleased to announce that the Journal has been accepted for indexing in Elsevier’s Scopus database. Currently used by over 3,000 academic, government, and corporate institutions, Scopus delivers a comprehensive overview of the world's research output in the fields of science, technology, medicine, social sciences, and arts and humanities.

JITC content will be available in Scopus within the next few weeks and the content will be indexed retroactively, meaning that all articles dating to the first issue will be included. This increased discoverability of JITC’s outstanding content speaks to its emergence as an eminent vehicle for publishing the most important content in the cancer immunotherapy field.

Case Report

Systemic inflammation in a melanoma patient treated with immune checkpoint inhibitors—an autopsy study Viktor H. Koezler, Sacha L. Rothschild, Deborah Zikler, Andreas Wicki, Berenila Willi, Neils Willi, Michèle Voegeli, Gieri Cathomas, Alfred Zippelius and Kirsten D. Mertz Journal for ImmunoTherapy of Cancer 2016, 4:13 (15 March 2016)

From the Authors
"Previous reports of immune-related adverse events in patients treated with immune-checkpoint inhibitors are predominantly based on clinical, laboratory and radiographic evidence. Here we present the first post-mortem analysis of immune pathology following sequential treatment with ipilimumab and nivolumab. This case identifies clinically unexpected treatment-related unfavorable medical occurrences and underlines the role of autopsy studies as an important measure of quality control." - Kirsten Mertz, MD, PhD – Cantonal Hospital Baselland, Institute of Pathology

Commentary

A role for pre-mNK cells in tumor progression Carolyn Rosinsky and Paul Andrew Antony Journal for ImmunoTherapy of Cancer 2016, 4:16 (15 March 2016)

From the Authors
"Pre-mNK cells, originally called Interferon Killer Dendritic Cells (IKDCs), have the potential to destroy cancer cells and to suppress anti-tumor immunity and autoiummune disease Recent evidence suggests that their natural function is to suppress anti-immunity as their removal can enhance cancer therapy and prevent recurrence of melanoma." - Paul Andrew Antony, MD – University of Maryland School of Medicine

Research Articles

Phase I study with ONCOS-102 for the treatment of solid tumors - an evaluation of clinical response and exploratory analyses of immune markers Tuuli Ranki, Sari Pesonen, Akseli Hemminki, Kaarina Partanen, Kalevi Kairemo, Tuomo Alanko, Johan Lundin, Nina Linder, Riku Turkki, Ari Ristimäki, Elke Jäger, Julia Karbach, Claudia Wahle, Matti Kankainen, Charlotta Backman, Mikael von Euler, Elina Haavisto, Tina Hakonen, Raita Heiskanen, Magnus Jaderberg, Juuso Juhila, Petri Priha, Laura Suoranta, Lotta Vassilev, Anti Vuolanto and Timo Joensuu Journal for ImmunoTherapy of Cancer 2016, 4:17 (15 March 2016)

From the Authors
"Local treatment with immune activating adenovirus ONCOS-102 in phase 1 trial resulted in prominent infiltration of CD8+ T cells to tumors, up-regulation of PD-L1 and induction of systemic tumor-specific CD8+ T cell responses in the last line cancer patients. Results highlight the potential of ONCOS-102 as an immunosensitizing agent for combinatory therapies with checkpoint inhibitors.” -
Sari Pesonen, PhD – Oncos Therapeutics

Systemic versus local responses in melanoma patients treated with talimogene laherparepvec from a multi-institutional phase II study Howard L. Kaufman, Thomas Amatruda, Tony Reid, Rene Gonzalez, John Glaspy, Eric Whitman, Kevin Harrington, John Nemunaitis, Andrew Zloza, Michael Wolf and Neil Senzer Journal for ImmunoTherapy of Cancer 2016, 4:12 (15 March 2016)

From the Authors
"Oncolytic viruses, such as talimogene laherprepvec (Imlygic), are a new treatment option for patients with melanoma. In this manuscript, we explored the pattern of clinical response observed with Imlygic in a phase II melanoma clinical trial. While we observed regression of both injected and un-injected lesions, the response rate was higher and occurred more quickly in directly injected lesions. These data have implications for clinical application of Imlygic, and perhaps other oncolytic viruses, which may be particulalry useful for locoregional disease and better used in combination approaches for more widespread disease as is being explored in several clinical trials.” - Howard L. Kaufman, MD, FACP – Rutgers Cancer Institute of New Jersey

Reviews

From bench to bedside a comprehensive review of pancreatic cancer immunotherapy Paul R. Krunk, Todd W. Bauer, Craig L. Slingluff and Osama E. Rahma Journal for ImmunoTherapy of Cancer 2016, 4:14 (15 March 2016)

From the Authors
“In this review, we detail the mounting evidence that the pancreatic cancer microenvironment is in a dynamic interaction between a variety of immune cells and cancer cells. The bench side discoveries of this interaction are currently being translated to the clinic with a plethora of immunotherapy clinical trials in pancreatic cancer.”
- Osama E. Rahma, MD – University of Virginia

Immunodynamics: a cancer immunotherapy trials network review of immune monitoring in immuno-oncology clinical trials Holbrook E. Kohort, Paul C. Tumeh, Don Benson, Nina Bhardwaj, Joshua Brody, Silvia Formenti, Bernard A. Fox, Jermone Galon, Carl H. June, Michael Kalos, Ilan Kirsh, Thomas Kleen, Guido Kromer, Jeffery Miller, Ignacio Melero, Kunle Odunsi, Karolina Palucla, George Peoples, Antoni Ribas, Harlan Robins, William Robinson, Tito Serafini, Paul Sondel, Eric Vivier, Jeff Weber, Jedd Wolchok, Laurence Zitvogel, Mary L. Disis, Martin Cheever, and on behalf of the Cancer Immunotherapy Trials Network (CITN) Journal for ImmunoTherapy of Cancer 2016, 4:15 (15 March 2016)

From the Authors "Technologic advances and the development of immune therapies that induce clinical responses in a majority of patients with specific tumor types has underscored the need for a broad based approach to immunologic monitoring. To capture the most important elements influencing therapeutically effective immunity, assays that explore both the tumor microenvironment and the effector immune response are needed. This paper reviews the current state of the art of measurable immune endpoints." - Mary L. Disis, MD, FACP – University of Washington Short Report

Immune Monitoring Technology Primer: Immunoprofiling of Antigen-stimulated blood Laura Rosa Brunet, Samuel LaBrie and Thorsten Hagermann Journal for ImmunoTherapy of Cancer 2016, 4:18 (15 March 2016)

From the Authors "Using whole blood, the TruCulture® system permits investigation of immunological activity following immune stimulation resulting in synthesis of a variety of immunological mediators and for their accumulation for more robust measurements. This research tool is not taxing for patients as only small blood volumes are required and is easily integrated with routine clinical sample processing as it only requires minimal handling." - Laura R. Brunet, DSc – Immoludon Therapeutics Ltd. Submit your Research to JITC Society for Immunotherapy of Cancer (SITC) members and non-members alike are invited to submit manuscripts to SITC's official journal. Journal Sections Basic Tumor Immunology Case Reports Clinical/Translational Cancer Immunotherapy Clinical Trials Monitor Commentary/Editorials  Immunotherapy Biomarkers Reviews JITC Editor-in-Chief Pedro J. Romero, MD – University of Lausanne Section Editors Lisa H. Butterfield, PhD – University of Pittsburgh Cancer Institute Christian Capitini, MD – University of Wisconsin - Madison Leisha Emens, MD, PhD – Johns Hopkins University Bernard A. Fox, PhD – Earle A. Chiles Research Institute, Providence Cancer Center Thomas F. Gajewski, MD, PhD – University of Chicago F. Stephen Hodi, Jr., MD – Dana-Farber Cancer Institute Cornelis J.M. Melief, MD, PhD – ISA Therapeutics BV Alfred Zippelius, MD – University Hospital Basel To view the full editorial board, please visit: immunotherapyofcancer.org/about/edboard. SITC Members Receive Complimentary Article Processing Charges in 2016 As a thank you to our members, SITC is offering complimentary article processing charges extended throughout 2016 (a $2,500 USD savings). For your membership code, contact the SITC office at +1 (414) 271-2456.

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