Toxicity of a monoclonal F(ab')2:ricin A conjugate for retinoblastoma in vitro

The toxic A chain of the poison ricin has been conjugated to the F(ab')2 fragment of a retinoblastoma-specific murine monoclonal antibody. The conjugate was toxic in vitro to Y-79 retinoblastoma cells at a concentration of approximately 5 X 10(-10) M; Y-79 retinoblastoma cells were the immunizing cells in the production of the monoclonal antibody. Against a second retinoblastoma cell line, the conjugate was toxic at a concentration of approximately 10(-9) M. Ricin A chain alone was not toxic to either of these cell lines at concentrations less than 4 X 10(-8) M. The conjugate was no more toxic than was ricin A chain against five control cell lines in vitro. The effect of the conjugate on retinoblastoma-derived cells was concentration dependent. Concentrations less than a "minimum" concentration were not cytotoxic, despite an excess of conjugate molecules over target cells. Concentrations greater than the minimum toxic concentration rapidly reached maximal toxicity, suggesting that antigenic sites were saturated. No clinical, hematologic, or renal toxicity was noted when mice were given injections of the conjugate at 1 mg/kg, or free ricin A chain at 0.375 mg/kg.