Simultaneous activation of T cells and accessory cells by a new class of intact bispecific antibody results in efficient tumor cell killing

Bispecific Abs (bsAb) are promising immunological tools for the elimination of tumor cells in minimal residual disease situations. In principle, they target an Ag on tumor cells and recruit one class of effector cell. Because immune reactions in vivo are more complex and are mediated by different cl asses of effector cell, we argue that conventional bsAb might not yield opt imal immune responses at the tumor site. We therefore constructed a bsAb th at combines the two potent effector subclasses mouse IgG2a and rat IgG2b, T his bispecific molecule not only recruits T cells via its one binding arm, but simultaneously activates Fc gamma R+ accessory cells via its Fc region, We demonstrate here that the activation of both T lymphocytes and accessor y cells leads to production of immunomodulating cytokines like IL-1 beta, I L-2, IL-6, IL-12, and DC-CK1, Thus this new class of bsAb elicits excellent antitumor activity in vitro even without the addition of exogenous IL-2, a nd therefore represents a totally self-supporting system.