Bispecific IgG and IL-2 therapy of a syngeneic B-cell lymphoma in immunocompetent mice.

Bispecific antibody (bsAb) which binds to CD3 and a tumor-associated antigen can induce lysis of tumor cells by T cells. Lymphocytes targeted by bsAbs are also capable of inhibiting the growth of human xenografts in athymic mice. However, little is known about the impact of this form of therapy in immunologically intact animals. The 38C13 murine B-cell lymphoma model is well suited for the study of bsAb therapy. BsAb, consisting of an IgG that is monospecific for both CD3 and the idiotype expressed by V 38C13 cells, was obtained from hybrid-hybridoma supernatant. Immunocompetent C3H mice were inoculated with V 38C13 cells and treated 2 days later with antibody. Over 90% of mice treated with monospecific antibody died of lymphoma, while only 27% of mice treated with bsAb developed tumor and died. In studies of bsAb/IL-2 synergy, treatment was delayed until 5 days after inoculation to allow for a larger tumor burden at the time of treatment. IL-2 was administered on days 3 to 6. All mice treated with IL-2 alone died of lymphoma, as did 75% of mice treated with bsAb alone. Only 18% of mice treated with both bsAb and IL-2 developed lymphoma. Thus, therapy with bsAb and IL-2 eliminated a tumor load 100- to 1000-fold greater than can be eliminated by therapy with anti-tumor antibody alone. These studies demonstrate the value of using immunocompetent animal models, and support the further exploration of bsAbs as an immunotherapy for human malignancy.