Hematopoietic progenitor kinase 1 (HPK1) is a protein kinase that reduces the T cell response to tumor cells. Specifically, HPK1 is a negative regulator of T cell receptor (TCR) signaling. Active HPK1 phosphorylates a protein in the TCR complex, flagging it for degradation, and blocking the TCR signaling important for mounting an immune response against tumor cells.
By inhibiting HPK1 with a small molecule compound it may be possible to enhance T cell function and antitumor responses. We are developing a series of small molecules that inhibit HPK1 and are currently preparing them for preclinical testing.