Jenna Newman, PhD, Lloyd J. Old Fellow

While cancer immunotherapy has significantly reduced cancer deaths, it remains ineffective for the majority of patients. T cells are often critical for immunotherapy success; T cells recognize pathogen-infected or abnormal cells, such as tumor cells, with high specificity, and subsequently kill such cells. Adoptive cell transfer (ACT) is an immunotherapy that involves transfer of tumor-reactive T cells to patients. Currently, there is highly variable success of ACT in the clinic, in part due to heterogeneity in strength of T cell-mediated recognition of tumors and in abundance of target expression by tumors. Neoantigens are mutant protein segments (peptides) that are unique to tumors, but are not abundant in the tumor. Conversely, tumor-associated antigens (TAAs) are peptides derived from healthy tissue, but are overexpressed in tumors. The goal of Dr. Newman’s proposed research is to determine whether neoantigen-targeting vs TAA-targeting T cells differentially impact ACT outcome. Further, she will interrogate the roles of neoantigen/TAA expression level by tumors and strength of T cell recognition of targets as factors that may individually and combinatorially impact ACT outcome. Additionally, she acknowledges that ACT success is additionally hindered by the inability to sustain T cell responses in the long-term. To address this, she will investigate combining ACT with interventions that boost dendritic cell function. Dendritic cells are critical players in processing neoantigens and TAAs and displaying them to T cells, the latter of which become primed and can exert anti-tumor activities. Ultimately, Dr. Newman seeks to characterize novel combinatorial paradigms that optimize ACT success.

Projects and Grants

Characterization of antigen quality, antigen quantity, and the tumor microenvironment as determinants of success of tumor-reactive CD8+ T cell adoptive cell transfer

Icahn School of Medicine at Mount Sinai | All Cancers | 2022 | Nina Bhardwaj, M.D. Ph.D.