June JITC Articles Now Available!

Letter from the Editor

Dear JITC Readers:

June has been an eventful month in the field of cancer immunology and immunotherapy. Earlier this month, the American Society of Clinical Oncology (ASCO) held its Annual Meeting in Chicago, Illinois. Attended by approximately 40,000 experts devoted to clinical oncology research, nearly one-third of the research presented was specific to immunotherapy. In addition, as you may know, in recent years June has been known as Cancer Immunotherapy Month and, although it is late in the month, SITC still has several ways you can commemorate this month by taking part in its educational programs. Click here for further information.

In addition to SITC’s unwavering commitment to finding a cure for cancer through its efforts in education and translational research, this month’s issue of JITC features a Commentary authored by SITC leadership on proposed changes to the Common Rule, which is a set of ethical principles that provide guidance on the management of human subjects taking part in biomedical and behavioral research in the United States. Recently, the US government has suggested a revision of the Common Rule to include more contemporary and streamlined oversight of clinical research. This thought-provoking Commentary provides valuable feedback on the proposed changes and suggests recommendations on further actions while supporting continued discussion with all stakeholders.

Moreover, this month’s issue features five research articles, one case report and two additional commentaries. J W.-L. Eng and colleagues examine the efficacy of an anti-DR5 monoclonal antibody to target pancreatic cancer stem cells (CSC) in patient-derived pancreatic tumor xenografts. Interestingly, they conclude that treatment of pancreatic tumors with anti-DR5 antibody can lead to durable tumor control by targeting both bulk tumor cells and CSCs. H. J. Gray and colleagues report the results of a randomized phase 2 clinical trial of therapeutic vaccination using CVac, a mucin 1 dendritic cell vaccine, as a maintenance therapy in patients with advanced ovarian carcinoma in first or second clinical remission. Progression free survival was longer in the second remission patient group than in the first remission as compared to patients randomized to standard of care only. In another original research report J. J. Luke and collaborators use state of the art immunomonitoring to assess the impact of denileukin diftitox, a recombinant fusion protein of human IL-2 and a diphtheria toxin fragment, on the priming of peptide-based vaccine specific T cell responses in melanoma in the context of a randomized phase II clinical trial. In contrast to other clinical studies, their results fail to indicate that diftitox effectively deplete regulatory T cells. In addition, it did not lead to augmentation of specific T cell responses nor improve clinical efficacy.

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

Case Report

Acute rhabdomyolysis with severe polymyositis following ipilimumab-nivolumab treatment in a cancer patient with elevated anti-striated muscle antibody Mehmet Asim Bilen, Sumit K. Subudhi, Jianjun Gao, Nizar M. Tannir, Shi-Ming Tu and Padmanee Sharma Journal for ImmunoTherapy of Cancer 2016, 4:36 (21 June 2016)

From the Authors
“We describe the first case of a patient with metastatic urothelial carcinoma who developed acute rhabdomyolysis with severe polymyositis after treatment with combination immunotherapy consisting of ipilimumab plus nivolumab, and retrospectively found to have an elevated pre-existing anti-striated muscle antibody titer. This case suggests that immune-related adverse events may be linked to subclinical autoimmune conditions which highlights the need for additional studies to identify patients who are at risk for toxicities.”
- Mehmet Asim Bilen, MD – MD Anderson Cancer Center

Commentary

Immune-related response evaluations during immune-checkpoint inhibitor therapy: establishing a “common language” for the new arena of cancer treatment Mizuki Nishino Journal for ImmunoTherapy of Cancer 2016, 4:30 (21 June 2016)

From the Author
"This article is a commentary on the recent JCO article by Hodi et al that evaluated atypical response patterns using immune-related response criteria in 327 melanoma patients treated with PD-1 inhibitor pembrolizumab therapy. The commentary discusses the key observations in the study in terms of their implications and pitfalls, emphasizes the important role of tumor response criteria as a “common language”, and discusses future directions for further advances of cancer immunotherapy.”
- Mizuki Nishino, MD, MPH – Dana-Farber Cancer Institute

How do I steer this thing? Using dendritic cell targeted vaccination to more effectively guide the antitumor immune response with combination immunotherapy Stefanie N. Linch and William L. Redmond Journal for ImmunoTherapy of Cancer 2016, 4:31 (21 June 2016)

From the Authors
"Our research suggests that combined checkpoint blockade and co-stimulatory molecule agonism can be insufficient to induce tumor regression. Instead, strategies incorporating vaccination against a tumor-associated antigen are vital to reversing CD8 T cell anergy. This triple combination can effectively direct antigen-specific T cell responses against the tumor to improve tumor regression and enhance survival.”
- William L. Redmond, PhD – Earle A. Chiles Research Institute

Society for immunotherapy of cancer (SITC) statement on the proposed changes to the common rule Howard L. Kaufman, Lisa H. Butterfield, Pierre G. Coulie, Sandra Demaria, Robert L. Ferris, Jérôme Galon, Samir N. Khleif, Ira Mellman, Pamela S. Ohashi, Willem W. Overwijk, Suzanne L. Topalian and Francesco M. Marincola Journal for ImmunoTherapy of Cancer 2016, 4:37 (21 June 2016)

From the Authors
"As a leading professional organization, SITC applauds the mandate to re-examine the Common Rule which governs how we ethically conduct clinical research in the United States. Given the progress in developing new treatment options for cancer patients, it is timely to re-consider the patient consenting process. SITC leadership, however, wants to reiterate the Society’s support of ethical principles in conducting clinical trials but also wants to ensure a fair and open dialogue on these complex issues in order to avoid an interruption in the successful implementation of clinical research at this pivotal point in cancer history.”
- Howard L. Kaufman, MD, FACS – Rutgers Cancer Institute of New Jersey

Research Articles

Effects of definitive chemoradiation on circulating immunologic angiogenic cytokines in head and neck cancer patients Vishwajith Sridharan, Danielle N. Margalit, Stephanie A. Lynch, Mariano Severgnini, F. Stephen Hodi, Robert I. Haddad, Roy B. Tishler and Jonathan D. Schoenfeld Journal for ImmunoTherapy of Cancer 2016, 4:32 (21 June 2016)

From the Authors
"Chemoradiation has complex effects on anti-tumor immunity and may impact immune suppressing angiogenic cytokines such as vascular endothelial growth factor (VEGF). In this prospective study of patients with squamous cell carcinoma of the head and neck, we observed significant changes in circulating levels of angiogenic cytokines over the course of definitive chemoradiation that could inform combined treatment approaches."
- Jonathan D. Schoenfeld, MD, MPH – Harvard Medical School

Pancreatic cancer stem cells in patient pancreatic xenografts are sensitive to drozitumab, an agonistic antibody against DR5 Jason W.-L. Eng, Thomas A. Mace, Rohit Sharma, Danielle Y. F. Twum, Peng Peng, John F. Gibbs, Rosemarie Pitoniak, Chelsey B. Reed, Scott I. Abrams, Elizabeth A. Repasky and Bonnie L. Hylander Journal for ImmunoTherapy of Cancer 2016, 4:33 (21 June 2016)

From the Authors
"Cancer stem cells (CSCs) can survive standard treatments that kill differentiated bulk tumor cells and are thought to play a critical role in recurrence. We found that the antibody (drozitumab) which targets the death receptor DR5, not only prevents tumor initiation by CSCs in vivo, but in vitro, it depletes DR5 expressing cells. DR5 is subsequently re-expressed by the remaining cells, sensitizing them to further anti-DR5 treatment. Since DR5 is a receptor for the immune effector molecule TRAIL, this work shows that immunotherapies targeting DR5 (ligands or TRAIL expressing immune cells) may be able to target both CSCs and differentiated tumor cells."
- Bonnie L. Hylander, PhD – Roswell Park Cancer Institute

Progression-free and overall survival in ovarian cancer patients treated with CVac, a mucin 1 dendritic cell therapy in a randomized phase 2 trial H. J. Gray, B. Benigno, J. Berek, J. Chang, J. Mason, L. Mileshkin, P. Mitchell, M. Moradi, F. O. Recio, C. M. Michener, A. Alvarez Secord, N. E. Tchabo, J. K. Chan, J. Young, H. Kohrt, S. E. Gargosky and J. C. Goh Journal for ImmunoTherapy of Cancer 2016, 4:34 (21 June 2016)

From the Authors
"CVac represents the first dendritic-cell vaccine / immunotherapeutic approach in epithelial ovarian cancer which is shown in our trial to have the potential of maintaining remission and prolonging survival in a subset of patients with recurrent ovarian cancer in second remission. The data is certainly encouraging and hypothesis generating. It would support further development of Cvac in the treatment paradigm of epithelial ovarian cancer, either alone or in combination with other newer immunotherapeutic agents that are synergistic in their effect."
- J. C. Goh, MBBS, FRACP – Greenslopes Private Hospital

Phenotypic and functional testing of circulating regulatory T cells in advanced melanoma patients treated with neoadjuvant ipilimumab Janet Retseck, Robert VanderWeele, Hui-Min Lin, Yan Lin, Lisa H. Butterfield and Ahmad A. Tarhini Journal for ImmunoTherapy of Cancer 2016, 4:38 (21 June 2016)

From the Authors
"In this study of melanoma patients, we used flow cytometry to evaluate the degree of regulatory T cell (Treg) frequency and proliferation suppression following treatment with ipilimumab at 10 mg/kg. We found that Treg frequency measures do not correlate with suppressive activity measured ex vivo while Treg suppressive activity increases correlate with poorer patient outcomes."
- Ahmad A. Tarhini, MD, PhD – University of Pittsburgh Cancer Institute

Research Articles

Single dose denileukin diftitox does not enhance vaccine-induced T cell responses or effectively deplete Tregs in advanced melanoma: immune monitoring and clinical results of a randomized phase II trial Jason J. Luke, Yuanyuan Zha, Karen Matijevich and Thomas F. Gajewski Journal for ImmunoTherapy of Cancer 2016, 4:35 (21 June 2016)

From the Authors
"Regulatory T cells (Tregs) are an important negative regulator of anti-tumor immunity. Targeting CD25 with denileukin diftitox has been promoted as one strategy for depleting Tregs in vivo. However, in the current report we provide evidence not only that denileukin diftitox did not deplete Tregs, but that it appeared to reduce vaccine-induced CD8+ T cell responses. Other more selective Treg-inhibitory strategies should be developed."
- Thomas F. Gajewski, MD, PhD – University of Chicago

May Highly
Accessed Articles

Can abscopal effects of local radiotherapy be predicted by modeling T cell trafficking?
Sandra Demaria and Silvia C. Formenti
Journal for ImmunoTherapy of Cancer 2016 4:29 (17 May 2016)

Glimpse into the future: harnessing autophagy to promote anti-tumor immunity with the DRibbles vaccine
David B. Page, Tyler W. Hulett, Traci L. Hilton, Hong-Ming Hu, Walter J. Urba and Bernard A. Fox
Journal for ImmunoTherapy of Cancer 2016 4:25 (17 May 2016)

2016 JITC Best Paper Awards: Submit Now

SITC will once again be offering two $1,000 USD awards for the best papers submitted in the Clinical/Translational and Basic Science categories. To be eligible, papers must be published in JITC by August 18, 2016. Recipients of the award will be highlighted in various SITC communications and recognized in front of their peers at SITC's 31st Annual Meeting & Associated Programs. For more information, including eligibility requirements, click here.

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