Potent synergy between KIT-targeted inhibitor dasatinib and agonist anti-OX40 mAb to eradicate P815 KIT-mutated mastocytoma tumors. (1) P815 KIT-mutated mastocytoma are sensitive to dasatinib leading to tumor cell death. (2) Cell debris are phagocytosed by DCs. (3) Dasatinib blocks Treg expansion possibly through LcK inhibition. (4) This results in CD4 T cell–dependent, tumor antigen–specific CD8/CTL activation and proliferation through antigen presentation by DCs. (5) Agonist OX40 mAb blocks Treg suppressive function. (6) Antigen-specific CTLs are OX40⁺ and engagement of OX40 leads to strong amplification of the activated antigen-specific CD8 pool and long-term maintenance of CD8 memory. (7) Tumor antigen–specific CD8 memory T cells detect and eradicate remaining tumor cell clones, even KIT loss variant emerging during targeted therapy, resulting in complete tumor eradication.