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Targeting the Immunosuppressive Tumor Microenvironment with Transform Switch Receptors (TSR)

Targeting the immunosuppressive tumor microenvironment with Transform Switch Receptors

Adoptive cell therapy (ACT) is an exciting therapeutic strategy that uses genetically-engineered immune cells to target and destroy tumors. The tumor microenvironment (TME) features obstacles that block T cells from eradicating tumor, such as the expression of inhibitory ligands, lack of positive signals, and tumor cells that compete with T cells for nutrients.

To “armor” T cells against these inhibitory hurdles, we innovate fusion proteins that combine a membrane-bound protein ectodomain with a costimulatory signaling endodomain. These novel proteins are expressed in genetically engineered T cells, for use in cell therapy. Our Transform Switch Receptors (TSRs) incorporate the ectodomain of a negative receptor that would normally shut down the T cell, with an intracellular costimulatory domain that provides a positive signal; thus, converting a negative signal to a positive signal. This approach combines a decoy receptor with a costimulatory signaling domain, to “replace a brake with an accelerator”.

We are developing a toolbox of TSRs and will determine which ones best enhance therapeutic efficacy against hematological and solid tumors, to support clinical translation.

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