Photoimmunotherapy: treatment of animal tumors with tumor-specific monoclonal antibody-hematoporphyrin conjugates

Abstract

The term "photoimmunotherapy" describes an anti-cancer treatment that combines the phototoxic effects of chemical such as hematoporphyrin and the target-seeking ability of antibodies. Hematoporphyrin was chemically coupled to monoclonal antibodies directed to the DBA/2J myosarcoma M-1. Administration of anti-M-1-hematoporphyrin conjugates i.v. to M-1 tumor-bearing animals followed by exposure to incandescent light resulted in suppression of M-1 growth. The time interval between injection and light exposure was an important parameter in terms of tumor suppression. Tumor-bearing animals maintained in the dark for 96 to 196 hr after hematoporphyrin-antibody injection followed by 4-hr light exposure demonstrated significantly lower tumor incidence and longer latency periods, in comparison to conjugate-treated animals instantly exposed to light. The growth inhibiting properties of the conjugate appeared to be M-1-specific; it had no effect on the growth of a C57BL/6J lymphoma EL4. In addition, conjugates made with a nonspecific monoclonal antibody did not have any specific anti-tumor effect on M-1 growth. Treatment with equivalent doses of hematoporphyrin or antibody had no significant inhibiting effect on tumor growth. Clearly, the homing ability of the specific monoclonal antibody-hematoporphyrin conjugate was essential for effective drug delivery and inhibition of tumor growth.