Amelioration of experimental lung metastasis in mice by therapy with anti-CD3 monoclonal antibodies

Abstract

Binding of CD3-specific antibodies to the TcR-CD3 complex results in T cell activation without the need for occupation of the T cell receptor (TcR) by its ligand. Murine T cells activated in this manner will kill a broad range of tumor targets but not normal lymphoblasts. We report here that non-specific cytolytic activity can be induced in vivo by a single i.p. injection of nonlytic 145-2C11 anti-CD3 monoclonal antibody. At least three populations of effector cells are activated in these mice. These are non-MHC (major histocompatibility complex) restricted cytotoxic T lymphocytes, activated natural killer cells, and lymphokine-activated killer cells. Anti-CD3 treatment is effective in significantly reducing the number of lung tumor nodules which form in mice inoculated with oncogenic ras-transfected syngeneic 10T1/2 fibroblasts. Anti-CD3-activated killer cells may, therefore, find a future role in cancer immunotherapy.