T cell-mediated depletion of intratumoral regulatory T cells using a CCR8xCD3 T cell-engaging bispecific antibody (TCB) promotes antitumor immunity in preclinical mouse models.

CCR8xCD3 T cell-engaging bispecific antibody (TCB) selectively depletes CCR8-expressing intratumoral regulatory T cells and inhibits tumor growth in multiple syngeneic mouse models.

• Why it matters: Solid-tumor TCBs have mainly targeted tumor cells, but immunosuppressive T reg cells in the tumor microenvironment can blunt antitumor immunity.
• What they did: The authors developed a CCR8xCD3 TCB and tested T cell–mediated depletion in vitro using human solid tumor samples, then evaluated tumor growth inhibition in syngeneic models and durability in cynomolgus monkeys.
• The result: The TCB depleted intratumoral T reg cells in vitro and mediated tumor growth inhibition alone or with anti-PD-L1, while in cynomolgus monkeys it was well tolerated and produced effective, durable depletion without acute phase inflammation or cytokine release syndrome.