JITC Digest July 2017

Inside this Issue:

Letter from the Editor

Dear JITC Readers:

This month, the nine articles published in the Journal for ImmunoTherapy of Cancer (JITC) explore an array of topics in cancer immunotherapy research. Among these are two special-interest articles: an in-depth report of SITC’s 2016 Annual Meeting, and an article exploring antigen-specific immunity and regulation as immune biomarkers of response to anti-tumor vaccines.

In “Highlights of the 31^st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), 2016,” the organizers of SITC’s 2016 Annual Meeting summarize the plenary sessions, presentations of emerging clinical and preclinical data, organizational and government initiatives, the tumor microenvironment, combination immunotherapy, and areas of challenge and opportunity in the field, both domestically and abroad. The report is organized by meeting session to help identify major themes and areas of interest for the reader.

Also this month, Laura E. Johnson and colleagues from the University of Wisconsin-Madison share a research article entitled “Pretreatment antigen-specific immunity and regulation - association with subsequent immune response to anti-tumor DNA vaccination.” Based on data from two previous phase I trials demonstrating an association between persistent PAP-specific Th1 immunity and favorable changes in serum PSA kinetics in patients with recurrent prostate cancer, the authors examined the role of antigen-specific or antigen non-specific immune parameters in the immune response to immunization. Results suggest that measures of antigen-specific regulation or tolerance may have value as positive (antigen-specific bystander suppression) or negative (antigen-specific IL-10 secretion) predictive biomarkers for immune response to immunization. The authors plan to investigate this prospectively in a phase II trial in patients with early, recurrent prostate cancer.

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

Case Report

Acute interstitial nephritis after sequential ipilumumab - nivolumab therapy of metastatic melanoma

Lea Bottlaender, Anne-Laure Breton, Louis de Laforcade, Frederique Dijoud, Luc Thomas and Stephane Dalle
Journal for ImmunoTherapy of Cancer 2017, 5:57 (18 July 2017)

Excerpt

"To our knowledge, this is the first case of nivolumab-induced acute interstitial immune nephritis. This case highlights that anti-PD-1 immunotherapy may be continued when renal function is adequate, and this requires close interaction between dermatologists and nephrologists."

Progressive hypoventilation due to mixed CD8⁺ and CD4⁺ lymphocytic polymyositis following tremelimumab - durvalumab treatment

Sooraj John, Scott J. Antonia, Trevor A. Rose, Robert P. Seifert, Barbara A. Centeno, Aaron S. Wagner and Ben C. Creelan
Journal for ImmunoTherapy of Cancer 2017, 5:54 (18 July 2017)

From the Authors

"Despite a dramatic regression in her cancer, our patient suffered an unusual neuromuscular complication from her anti-CTLA-4 and PD-L1 immunotherapy combo. On autopsy, we found this was due to a lymphocytic polymyositis of the diaphragm. More research is needed to describe the mechanism of drug-related autoimmune polymyositis. As clinicians, we must remain alert for these types of rare but serious side effects."

Ben C. Creelan, MD, MS — Moffitt Cancer Center

Regression of multifocoal in transit melanoma metastases after palliative resection of dominant masses and 2 years after treatment with ipilimumab

Raphael B. Moreira, Lana Hamieh, Evisa Gjini, Ana Lako, Katherine M. Krajewski, Charles H. Yoon and Patrick A. Ott
Journal for ImmunoTherapy of Cancer 2017, 5:61 (18 July 2017)

From the Authors

"This case of complete response of all skin metastases shortly after palliative resection of the dominant, symptomatic lesions in a melanoma patient who had received treatment with ipilimumab 2 years prior illustrates that melanoma-specific immune responses can be activated 1) by an external, presumably inflammatory stimulus 2) very late after CTLA-4 inhibition or 3) by a combination thereof."

Patrick A. Ott, MD, PhD — Dana-Farber Cancer Institute, Harvard Medical School

Angiosarcoma treated successfully with anti-PD-1 therapy – a case report

Simran Sindhu, Lana H. Gimber, Lee Cranmer, Ali McBride and Andrew S. Kraft
Journal for ImmunoTherapy of Cancer 2017, 5:58 (18 July 2017)

From the Authors

"Although sarcomas are not thought to be highly sensitive to immunotherapy, we report a case of an angiosarcoma patient who had failed standard therapy but had a complete response to anti-PD-1 therapy. This report suggests that testing angiosarcoma patients for PD-1 and PD-L1 expression may help in the decision to try immunotherapy."

Andrew S. Kraft, MD — The University of Arizona Cancer Center

Macrophage type 2 differentiation in a patient with laryngeal squamous cell carcinoma and metastatic prostate adenocarcinoma to the cervical lymph nodes

Michael C. Topf, Madalina Tuluc, Larry A. Harshyne and Adam Luginbuhl
Journal for ImmunoTherapy of Cancer 2017, 5:60 (18 July 2017)

From the Authors

"We describe a rare case of solitary metastatic prostate cancer to cervical lymph nodes in the setting of laryngeal cancer. The draining lymph nodes from the larynx showed an overwhelming number of CD163+, M2 macrophages compared to benign controls suggesting that lymph nodes can be 'primed' to the M2 phenotype leading to a higher risk of metastases from circulating tumor cells."

Michael C. Topf, MD — Thomas Jefferson University Hospital Department of Otolaryngology

Commentary

Transplanters drive CARs to the clinic by brewing ICE-T: the Moffitt roadmap

Frederick L. Locke, Claudio Anasetti for the Moffitt Immunotherapy Working Group and the Immune Cell Therapy (ICE-T) Program
Journal for ImmunoTherapy of Cancer 2017, 5:59 (18 July 2017)

From the Authors

"We describe our process for implementing a collaborative cross departmental Immune Cell Therapy (ICE-T) program to provide clinical care and trial coordination for immune cell therapies. Liquid and solid tumor principal investigators maintain oversight of these pivotal CAR-T, TCR and TIL trials. However, coordination and care is centralized to leverage the expertise and infrastructure of the Blood and Marrow Transplant program at Moffitt Cancer Center."

Frederick L. Locke, MD — H. Lee Moffitt Cancer Center and Research Institute

Research Article

Pretreatment antigen-specific immunity and regulation - association with subsequent immune response to anti-tumor DNA vaccination

Laura E. Johnson, Brian M. Olson and Douglas G. McNeel
Journal for ImmunoTherapy of Cancer 2017, 5:56 (18 July 2017)

From the Authors

"In this manuscript, we sought to identify immunological markers as possible predictors of immune response to anti-tumor DNA immunization in trials that used a DNA vaccine encoding the prostate tumor antigen prostatic acid phosphatase (PAP). While the study was small, we found that non-immune responders tended to have pre-existing PAP-specific T cells secreting IL-10, and immune responders had greater pre-existing PAP-specific regulatory cells detected by their ability to suppress DTH to a recall antigen."

Douglas G. McNeel, MD, PhD — University of Wisconsin Carbone Cancer Center

Review

Highlights of the 31^st Annual Meeting of the Society for Immunotherapy of Cancer (SITC), 2016

James L. Gulley, Elizabeth A. Repasky, Laura S. Wood and Lisa H. Butterfield
Journal for ImmunoTherapy of Cancer 2017, 5:55 (18 July 2017)

From the Authors

"This paper summarizes many of the sessions at last November’s SITC Annual Meeting. We had an exciting keynote from Ira Mellman on the mechanism of PD-1 pathway inhibition, and the Smalley Award presentation from Suzanne Topalian on clinical cancer immunotherapy. The latest studies on the tumor microenvironment, CAR T cells and bispecific antibodies, rational therapeutic combinations, and diet and exercise were discussed. From late-breaking abstracts to updates on many SITC initiatives, much of the state of the field was presented and are briefly presented in this meeting report."

Lisa H. Butterfield, PhD — UPMC Hillman Cancer Center

Colony-stimulating factor 1 receptor (CSF1R) inhibitors in cancer therapy

Michael A. Cannarile, Martin Weisser, Wolfgang Jacob, Anna-Maria Jegg, Carola H. Ries and Dominik Rüttinger
Journal for ImmunoTherapy of Cancer 2017, 5:53 (18 July 2017)

From the Authors

"In contrast to the current focus on T cell immunotherapies, the tumor-permissive and immunosuppressive characteristics of tumor-associated macrophages (TAM) only recently fueled interest in therapeutically targeting these cells. Several clinical studies are underway investigating the CSF1/CSF1R signaling pathway, which is known to be crucial for the survival and differentiation of tumor-promoting TAM. This review summarizes currently available safety and efficacy data for CSF1/CSF1R targeting agents and discusses the potential impact of organ-specific features of TAM."

Michael A. Cannarile, PhD — Roche Pharmaceutical Research and Early Development

June Highly Accessed Articles

New Cancer Immunotherapy Agents in Development: a report from an associated program of the 31^stAnnual Meeting of the Society for Immunotherapy of Cancer, 2016

Prasad S. Adusumilli, Edward Cha, Mark Cornfeld, Thomas Davis, Adi Diab, Thomas W. Dubensky Jr., Elizabeth Evans, Jane L. Grogan, Bryan A. Irving, Rom S. Leidner, Shane A. Olwill, Patrick Soon-Shiong, Frederic Triebel, David Tuck, Adrian Bot, Roger D. Dansey, Charles G. Drake, Gordon J. Freeman, Ramy Ibrahim, Salil Patel and Daniel S. Chen
Journal for ImmunoTherapy of Cancer 2017 5:50 (20 June 2017)

Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma

Anna Laurell, Maria Lönnemark, Einar Brekkan, Anders Magnusson, Anna Tolf, Anna Carin Wallgren, Bengt Andersson, Lars Adamson, Rolf Kiessling and Alex Karlsson-Parra
Journal for ImmunoTherapy of Cancer 2017 5:52 (20 June 2017)