Project Grant R01CA300792

Award Date 4/1/25
Completion Date 3/31/30
Dollars Obligated $710K
Federal Grant Program
93.395
Assistance Type
Project Grant
Place of Performance
Georgia, USA
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  1. Gain insights on how blocking the Semaphorin 4D (SEMA4D) protein, when combined with immune checkpoint blockade, affects the induction and infiltration of antigen-presenting cell types like dendritic cells and macrophages, and enhances B-T cell interactions in the tumor microenvironment.

  2. Use genetically diverse mouse models to explore the role of specific immune cell populations, including B cells, T cells, dendritic cells, and macrophages, in eliciting durable anti-tumor immunity when SEMA4D is blocked in combination with immune checkpoint inhibitors.

  3. Determine if targeting the LAG3 inhibitory checkpoint can serve as a more tolerable and effective alternative to CTLA-4 blockade to overcome resistance to SEMA4D/PD-1 therapy.

The research aims to uncover the mechanistic basis for how SEMA4D-targeting regimens sustain durable anti-tumor immunity and how this approach can be combined with LAG3 blockade for future clinical translation across solid tumors.

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