Intraperitoneal photoimmunotherapy of ovarian carcinoma xenografts in nudemice using charged photoimmunoconjugates

Objective. The objective of this study was to compare the efficacy of photo immunoconjugates with cationic and anionic molecular charges on intraperito neal photoimmunotherapy of ovarian cancer xenografts in nude mice. Methods. The photosensitizer chlorin(e6) (c(e6)) was conjugated via a poly- L-lysine linker to the F(ab')(2) fragment of the murine anti-ovarian cancer monoclonal antibody OC125, resulting in a photoimmunoconjugate with a pron ounced cationic charge. Alternatively, by succinylating the poly-L-lysine c onjugate, a photoimmunoconjugate with a pronounced anionic charge was obtai ned, A murine model of ovarian cancer derived from intraperitoneal inoculat ion of NIH:OVCAR-5 cells was employed. The conjugate was injected intraperi toneally followed after 3 h by red light delivered through a fiber into the peritoneal cavity, These photoimmunotherapy treatments were repeated three times, and the results obtained with the anionic and cationic photoimmunoc onjugates were compared with those obtained with free c(e6) and control. Th e extent of residual macroscopic disease and death from disease were the ev aluable outcomes for tumoricidal and survival studies, respectively. Results. In contrast to other intraperitoneal photosensitizers, mice showed no systemic toxicity or morbidity from the treatment. In this initial stud y the mean residual tumor weights in all treatment groups ranged from 33 to 73 mg, as compared with 330 mg in untreated controls (P < 0.0001), and the response to the cationic conjugate was significantly better than that to t he anionic conjugate or free c(e6) (P < 0.005), The median survival for mic e treated with cationic photoimmunoconjugate was 41 days, compared with 35 days in controls (P = 0.009). Conclusion. Photoimmunotherapy with a cationic photoimmunoconjugate produce s results superior to those obtained with an anionic conjugate, and further optimization of the treatment regimen may lead to a potential treatment fo r advanced ovarian cancer. (C) 2000 Academic Press.