JITC Digest June 2017

Inside this Issue:

Letter from the Editor

Dear JITC Readers:

The Journal for ImmunoTherapy of Cancer (JITC) joins the Society for Immunotherapy of Cancer (SITC) in recognizing Cancer Immunotherapy Month. In the June issue, JITC draws attention to key areas of cancer immunotherapy research that will inform ongoing developments in the field.

Of note, “New Cancer Immunotherapy Agents in Development: a report from an associated program of the 31^st Annual Meeting of the Society for Immunotherapy of Cancer, 2016” by Prasad S. Adusumilli et al. summarizes data from over a dozen rapid-fire presentations that were delivered by representatives from industry and academia at SITC’s 2016 Annual Meeting. Topics covered include cutting-edge cancer immunotherapy agents in development, and strategic considerations in development of combinations and biomarkers. Common themes identified include the need for a deeper understanding of the mechanisms by which current immunotherapies exert their effects, in order to drive rational development of monotherapy and combination strategies. There is also broad agreement that combination strategies are likely to yield the greatest clinical successes.

In “Adoptive cell therapy using PD-1⁺ myeloma-reactive T cells eliminates established myeloma in mice,” Bryon D. Johnson and colleagues explore the challenges of identifying and enriching appropriate T cell subsets for tumor eradication in hematologic cancers. After demonstrating that PD-1 is a biomarker for functional myeloma-specific T cells, the authors show that activated and expanded PD-1⁺ T cells can be effective as adoptive cellular therapy (ACT) for myeloma. These results, also shown in melanoma, suggest the value of this T cell sorting strategy for the treatment of other hematologic malignancies as well.

In “GITR ligand fusion protein agonist enhances the tumor antigen–specific CD8 T-cell response and leads to long-lasting memory," Nicholas Mason Durham et al. explore agonism of the glucocorticoid-induced tumor necrosis factor receptor family-related receptor (GITR) by GITRL-FP, a novel murine multimeric fusion protein capable of modulating GITR signaling on T cells. Their results have the potential to guide tumor indications or combinations where GITR agonism will be most successful, while also identifying key questions to address in human clinical trials of GITR.

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

JITC Welcomes James L. Gulley, MD, PhD, FACP to the Editorial Board

JITC is pleased to welcome Dr. James L. Gulley of the National Cancer Institute (NCI) as the new Section Editor for JITC’s Clinical/Translational Cancer Immunotherapy Section. Following the tenure of the influential founding Section Editor, Dr. F. Stephen Hodi, Jr., Dr. Gulley will lead one of the journal’s most popular sections during a time of exponential growth in cancer immunotherapy research.

Dr. Gulley currently serves as Chief of the Genitourinary Malignancies Branch of the Center for Cancer Research, as well as the Director of the Medical Oncology Service of the Office of the Clinical Director at the NCI. Dr. Gulley has led numerous cancer immunotherapy trials, including studies investigating cancer vaccines and other immunostimulatory agents and combinatorial strategies. Dr. Gulley played a central role in the clinical development of the prostate cancer vaccine, Prostvac, developed within the NCI, and serves as principal investigator on an international Phase III randomized clinical trial of this vaccine and on an international trial of an anti-PD-L1 antibody.

Please take a moment to congratulate and welcome Dr. Gulley through SITC CONNECT.

Case Report

Cerebral vasculitis mimicking intracranial metastatic progression of lung cancer during PD-1 blockade

Heinz Läubli, Jürgen Hench, Michal Stanczak, Ingmar Heijnen, Alexandros Papachristofilou, Stephan Frank, Alfred Zippelius and Frank Stenner-Liewen
Journal for ImmunoTherapy of Cancer 2017, 5:46 (20 June 2017)

From the Authors

"The case reports a severe complication of PD-1 blockade with the development of cerebral vasculitis due to pre-existent autoantibodies that posed diagnostic difficulties by mimicking intracranial metastatic progression. Immune-related adverse events that affect the central nervous system are rare but should be critically considered in the differential diagnosis."

Heinz Läubli, MD, PhD — University Hospital Basel

Nivolumab as salvage treatment in a patient with HIV-related relapsed/refractory Hodgkin lymphoma and liver failure with encephalopathy

Jose D. Sandoval-Sus, Francis Mogollon-Duffo, Ankita Patel, Nathan Visweshwar, Damian A. Laber, Richard Kim and Michael V. Jagal
Journal for ImmunoTherapy of Cancer 2017, 5:49 (20 June 2017)

From the Authors

"Patients diagnosed with advanced Hodgkin lymphoma that progress after autologous stem cell transplant or brentuximab vedotin have a dismal prognosis, with disease control of less than 4 months after subsequent therapies. Antibodies against PD-1 have demonstrated an impressive response rate of more than 65% in this patient population, which corresponds with the highest clinical activity of checkpoint inhibitors amongst any type of cancer treated with these novel agents. Nonetheless, patients diagnosed with HIV and/or AIDS, and subjects with liver dysfunction regardless of the etiology, have systematically been excluded from clinical trials with anti-PD1 inhibitors. Our case report exemplifies the safety and profound activity of checkpoint inhibition in a patient with both HIV/AIDS and liver failure, which is a common scenario in our clinical practice, and should motivate prospective clinical research of novel immunotherapies in patients with different types and severities of immunosuppression."

Jose D. Sandoval-Sus, MD — University of South Florida/Moffitt Cancer Center

Safe and effective administration of T-VEC in a patient with heart transplantation and recurrent locally advanced melanoma

Gustavo Schvartsman, Kristen Perez, Jill E. Flynn, Jeffrey N. Myers and Hussein Tawbi
Journal for ImmunoTherapy of Cancer 2017, 5:45 (20 June 2017)

From the Authors

"Patients who are recipients of solid organ transplantation require immune suppression and are often denied the use of cancer immunotherapy for fear of rejection of the transplanted organ. We safely and successfully treated a patient with a heart transplant and locally advanced unresectable melanoma with talimogene laherparepvec (T-VEC), which induced a complete response of the melanoma without any adverse impact on the transplanted heart."

Hussein A. Tawbi, MD, PhD — University of Texas-MD Anderson Cancer Center

Research Article

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)

From the Authors

"Our findings indicate that intratumoral administration of pro-inflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated."

Alex Karlsson-Parra, MD, PhD — Uppsala University

GITR ligand fusion protein agonist enhances the tumor antigen–specific CD8 T-cell response and leads to long-lasting memory

Nick M. Durham, Nick Holoweckyj, Randall S. MacGill, Kelly McGlinchey, Ching Ching Leow and Scott H. Robbins
Journal for ImmunoTherapy of Cancer 2017, 5:47 (20 June 2017)

From the Authors

"In this study, we examined how a multimeric GITR ligand fusion protein directly modulates tumor antigen specific CD8 T cells in murine models. Our results demonstrate that the delivery of GITRL-FP as a therapeutic can promote potent anti-tumor responses in the presence of tumor-specific CD8 T cells as well as provide hypotheses that can be tested in human clinical trials exploring GITR agonists including GITRL-FP."

Nicholas Durham, PhD — Medimmune

Adoptive cell therapy using PD-1⁺ myeloma-reactive T cells eliminates established myeloma in mice

Weiqing Jing, Jill A. Gershan, Grace C. Blitzer, Katie Palen, James Weber, Laura McOlash, Matthew Riese and Bryon D. Johnson
Journal for ImmunoTherapy of Cancer 2017, 5:51 (20 June 2017)

From the Authors

"We show that myeloma-reactive PD-1⁺ T cells can be activated to secrete Th1 cytokines and expand ex vivo. When administered as immunotherapy, ex vivo-expanded PD-1⁺ T cells persist in vivo and provide anti-myeloma immunity when combined with PD-L1/PD-1 blockade."

Bryon D. Johnson, PhD — Medical College of Wisconsin

Review

New Cancer Immunotherapy Agents in Development: a report from an associated program of the 31^st Annual 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)

From the Authors

"The emergence of PD-L1/PD-1 targeted therapies has finally validated the importance of the biologic interaction between a patient’s immune system and cancer. However, truly transformative benefit is still only experienced by a subset of patients treated with such therapies. It is our responsibility as a cancer immunology community to fulfill the promise of immunotherapy for patients – and we believe this will come from the development of novel immune combination regimens."

Daniel S. Chen, MD, PhD — Genentech

May Highly Accessed Articles

Identifying baseline immune-related biomarkers to predict clinical outcome of immunotherapy

Sacha Gnjatic, Vincenzo Bronte, Laura Rosa Brunet, Marcus O. Butler, Mary L. Disis, Jérôme Galon, Leif G. Hakansson, Brent A. Hanks, Vaios Karanikas, Samir N. Khleif, John M. Kirkwood, Lance D. Miller, Dolores J. Schendel, Isabelle Tanneau, Jon M. Wigginton and Lisa H. Butterfield
Journal for ImmunoTherapy of Cancer 2017 5:44 (16 May 2017)

Evaluation of dosing strategy for pembrolizumab for oncology indications

Tomoko Freshwater, Anna Kondic, Malidi Ahamadi, Claire H. Li, Rik de Greef, Dinesh de Alwis and Julie A. Stone
Journal for ImmunoTherapy of Cancer 2017 5:43 (16 May 2017)