Genentech Inc. presented data on structure-based lead optimization of orally bioavailable hematopoietic progenitor kinase 1 (HPK1) inhibitors. HPK1 is a negative regulator of T-cell receptor signaling in human T cells and target inhibition significantly increases cytokine production, such as IFN-gamma, TNF-alpha and IL-2, and T-cell proliferation, suggesting HPK1 inhibition as an intracellular T-cell target for cancer immunotherapy.