Novel Strategies for Combining Cancer Immunotherapies Highlighted at SITC 2014

November 4, 2014

NATIONAL HARBOR, MD – Experts at the Society for Immunotherapy of Cancer (SITC) Annual Meeting & Associated Programs have identified novel ways to combine cancer immunotherapies, which could open the door to increasing the number of cancer patients who respond to treatment.

“One of the most promising areas of clinical investigation has been in the arena of combining various types of immunotherapy. Early data suggests that this strategy may lead to additive or even synergistic therapeutic activity. While further studies are needed to better understand the benefit and potential toxicity of specific combinations, the use of combination therapy may provide significant benefit to a much larger number of cancer patients,” said SITC Vice President Howard Kaufman, MD.

As part of SITC’s Workshop on Combination Immunotherapy: Where Do We Go From Here?, Hassane Zarour, MD, will discuss targeting multiple inhibitory receptors to reverse T cell dysfunction caused by melanoma.

Research has shown that several dysfunctional tumor antigen-specific CD8+ and CD4+ T cell subsets found at periphery and tumor sites upregulate PD-1, BTLA and Tim-3 expression. PD-1, BTLA and Tim-3 help diminish tumor antigen-specific CD8+ and CD4+ T cell responses in advanced melanoma patients. Further, using monoclonal antibodies to target inhibitory receptors improves the expansion and functions of TA-specific CD8+ and CD4+ T cells. These findings support targeting PD-1, BTLA and Tim-3 as a way to reverse T cell dysfunction caused by melanoma and increase the chance that patients with advanced melanoma will see clinical benefits with their treatment.

Representing another novel strategy, F. Stephen Hodi, MD, will present on cytokine and anti-angiogenesis checkpoint combinations. Combining ipilimumab with blocking vascular endothelial growth factor (VEGF) has shown: improved lymphocyte trafficking across the thin layer of cells that line blood and lymph vessels, changes in circulating immune memory, and induction of antibodies to a number of immunogenic targets. This combination is currently being studied in a randomized Phase 2 study. Combining PD-1/PD-L1 antibodies and blocking VEGF is also being investigated.

Further, the role of cytokine interactions with these novel agents continues to progress. While not improving progression-free survival, a randomized Phase 2 study found that adding GM-CSF to ipilimumab improved overall survival as well as lowered the occurrence of high-grade adverse events.

To guide the development and clinical application of combination immunotherapy, attempts to immune-profile the tumor microenvironment are being investigated. Immune-profiling before treatment could lead to the identification of biomarkers that might predict what the response will be, while immune-profiling patients currently in treatment could lead to the identification of biomarkers that may indicate a favorable clinical response. Thus, immune-profiling could lead to early intervention and changing treatment routines in patients who may not be responding.

The SITC 29th Annual Meeting & Associated Programs takes place November 6-9, 2014 at the Gaylord National Hotel & Convention Center in National Harbor, MD. Find more information at:

About SITC
Founded in 1984, Society for Immunotherapy of Cancer (SITC) is a non-profit medical society dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy through the core values of interaction, innovation and leadership. For more information on SITC, visit the Society website at: