SPORE grant

The TMMC's research program is partially supported by the SPORE in Skin Cancer grant. 

The Wistar/University of Pennsylvania SPORE in Skin Cancer is the result of a decades-long collaboration between the two institutions in the effort to reduce the morbidity and mortality from skin cancer. The clinical landscape of melanoma has evolved rapidly over the last decade. Immune checkpoint inhibition has revolutionized melanoma therapy to the point where every high-risk melanoma patient will be treated at some point with these agents. However, many major questions remain on how best to use these immune therapeutics. This SPORE has three melanoma-focused projects:

Project 1: Exosomal PD-L1 in immune checkpoint inhibitor therapy. Project 1 addresses the unmet need to find an effective biomarker to select patients for single agent versus combination immunotherapy. Exosomal PD-L1 is an immunosuppressive factor secreted by melanomas. We propose rigorous clinical utility studies designed to demonstrate this blood-based measurement as a highly-sensitive and specific predictive biomarker for anti-PD-1 antibody (Ab)-based therapy.

Project 2: Targeting autophagy to improve immune checkpoint inhibition. Project 2 addresses a second unmet need for a safer and effective combination regimen that promises to be effective in anti-PD-1 Ab refractory patients. Based on extensive preclinical data and a new molecular target in the lysosome, we have developed a clinical trial of combined anti-PD1 Ab or anti-PD-1 and anti-CTLA-4 Ab and lysosomal autophagy inhibition, a new strategy for reprogramming tumor-associated macrophages to enhance the efficacy of T-cell killing.

Project 3: Neoadjuvant immunotherapy strategies for early-stage melanoma. Project 3 fills a major gap in the treatment of early disease by conducting a clinical trial with anti-PD1 Ab in stage IIB/C melanoma patients. Besides in-depth characterization of the immune response, the project’s preclinical studies will lead to new strategies for enhancing the immune stimulatory capacity of dendritic cells in the tumor microenvironment.

In addition to these 3 projects this SPORE has a well-developed Developmental Research Project Program and Career Enhancement Project Program. These pilot programs feed the sustainability of the SPORE and will have a special focus on non-melanoma skin cancers and the recruitment of underrepresented minorities into skin cancer research and skin cancer clinical trials.

The highly translational projects and pilot programs are supported by three cores:

Core A: Administrative Core
Core B: Biospecimen and Pathology Core
Core C: Biostatistics and Bioinformatics Core

Each year, the SPORE grant funds multiple Development Research Program and Career Enhancement Program projects. For more information, please contact Dr. Amaravadi or Jessica Kohn.