MRA awarded three outstanding young investigators $100,000 over two years whose work shows great promise in the field of melanoma research.
Targeting CD4+ T cells for melanoma immunotherapy
Timothy Bullock, Ph.D.
Assistant Professor, Department of Pathology, University of Virginia
Dr. Bullock has been working to optimize a vaccination strategy that elicits the highest magnitude helper T cell response to specific targets expressed by melanoma cells. Dr. Bullock also identified targets on “corrupted” T cells (helper T cells that have been converted to regulatory T cells that suppress immune response to the tumor) in order to disrupt their function or prevent the conversion from occurring. A combination approach that suppresses and bypasses regulatory mechanisms and supports survival of cells is necessary for eliciting large populations of CD4 cells. They have also found that the presence of these cells enhances the trafficking of cytotoxic T cells to the tumor.
Regulation of T cellchemokine receptor expression during vaccination: Tumor-targetedimmunotherapy
David Mullins, Ph.D.
Assistant Professor, Department of Microbiology and Human Immune Therapy, University of Virginia
Dr. Mullins confirmed that CXCR3 (a chemokine receptor previously found to be expressed on a subset of melanoma patients’ CD8 T cells) serves to assist these T cells in migrating into melanomas, and vaccination with melanoma-derived peptides and adjuvant can induce CXCR3-positive T cells in greater that 95 percent of patients. His lab discovered that cells can produce these chemical beacons following local administration of IFN-gamma. In part with funding by the NIH, Dr. Mullins will initiate a Phase I trial to assess the effects of dual administration of vaccination and IFN-gamma treatment of the tumor to optimize CD8 T cell tumor infiltration.
Publications:
- Interferons induce CXCR3-cognate chemokine production by human metastatic melanoma
Defining the role of inducible co-stimulator (ICOS)-expressing T cells against melanoma
Padmanee Sharma, M.D., Ph.D.
Assistant Professor, University of Texas, M.D. Anderson Cancer Center
Research indicates that patients who have improved survival after ipilimumab (anti-CTLA-4) treatment have sustained elevations of numbers of ICOS-expressing T cells. ICOS is a stimulatory co-regulator of T cell anti-tumor immune responses. To understand the role of these T cells in the anti-tumor response, studies conducted in mouse models showed that the ICOS pathway is necessary for optimal anti-tumor immune response.
Publications: