Monomeric bispecific F(ab)'2 antibodies were used to redirect the antigen specificity of T-lymphocytes from normal human donors, so that they became cytotoxic for an allogeneic ovarian carcinoma cell line. The altered lymphocytes killed the tumor cells in vitro and also blocked intraperitoneal growth of the tumor cells in immunodeficient mice, even though tumor growth was established prior to treatment. The antitumor effects in vivo were found both upon examining peritoneal lavage fluid 2 weeks after treatment and by monitoring host survival. Treatment of tumor-bearing mice, consisting of two injections spaced over four hours, doubled their mean survival time relative to controls. Bacterial lipopolysaccharide (LPS), including an attenuated form, was used to nonspecifically activate mouse cytotoxic T lymphocytes (CTL), which then were retargeted with bispecific antibodies to lyse syngeneic tumor cells in vitro. The activation process involved CD8+ cytolytic precursor cells, CD4+ T-helper cells, and accessory cells that, by radiation sensitivity, appeared to be B lymphocytes. Cell mixing experiments, using splenocytes from LPS-responsive and nonresponsive, MHC-matched mouse strains showed that the accessory cells were the main cellular target for LPS.
