Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by the clonal proliferation of dysfunctional B cells that crowd out healthy blood cells in the bone marrow and peripheral blood. Notwithstanding low mutational burden and an immunosuppressive tumor microenvironment, there is emerging evidence that anti-tumor immunity can play a role in influencing the natural history of CLL, and can potentially be harnessed for CLL therapeutics.
Specifically, there are rare instances of patients who undergo spontaneous regression of CLL, suggesting an immune phenomenon that underlies disease control. Pursuing this avenue in my research, this project aims to investigate whether a cancer vaccine approach has therapeutic potential in CLL, and delineate the determinants of response versus resistance in the context of vaccine therapies.
Using interferon gamma ELISpots and other functional assays, I will assess T cell responses and tumor-immune dynamics in the context of the GVAX (NCT00442130) and NeoVax (NCT03219450) clinical trials, both of which are vaccines that harness the immune system for the treatment of CLL. The NeoVax approach that aims at early CLL interception involves computational prediction of neoantigens derived from somatic mutations, which are incorporated as peptide-based vaccine targets to stimulate a durable immune response. Meanwhile, the GVAX approach involves directing a donor-derived immune system to produce leukemia-specific T-cells post-allogenic stem cell transplantation via whole tumor cell vaccination.
By understanding the immune mechanisms that underlie vaccine response versus resistance, we can potentially optimize personalized immunotherapeutic approaches for patients with CLL.
