Chronic Lymphocytic Leukemia (CLL) is a hematologic malignancy marked by the clonal expansion of transformed B cells that circulate across distinct compartments in the bone marrow, lymph nodes and peripheral blood. Despite its typically low mutational burden and immunosuppressive properties, emerging evidence suggests that CLL cells harbor multiple tumor-specific antigens, which could potentially allow the immune system to recognize and control CLL through eliciting a tumor-specific T cell response. These features make CLL an attractive target for immunotherapeutic approaches, particularly strategies aimed at reactivating and diversifying anti-tumor immune responses.
During the course of my co-op I will be mainly focused on the immune monitoring aspect of two clinical trials of personalized cancer vaccines for CLL treatment, namely, NeoVax (NCT03219450) and GVAX (NCT00442130). NeoVax is a personalized mutli-valent neoantigen vaccine for the early interception of high risk CLL that involves the targeting up to 20 tumor-specific neoantigens. GVAX was a whole tumor cell vaccine which was previously administered in the context of relapse refractory CLL who underwent an allogenic stem cell transplant.
My research focuses on evaluating the therapeutic potential of cancer vaccines in CLL and identifying the immune-related factors that differentiate those who achieve a sustained response in treatment, from those who fail to respond or subsequently relapse. In the context of NeoVax, I will further investigate the effects of the addition of low-dose cyclophosphamide (for regulatory T cell suppression) and/or pembrolizumab (a PD-1 inhibitor that reverses T cell exhaustion) on its ability to modulate vaccine-induced T cell responses. For my investigation, I will utilize a range of techniques including interferon gamma ELISpots, flow cytometry, and other functional assays to analyze T cell responses and their interaction with tumor cells in disease and healthy states.
Northeastern University
