Combination photoimmunotherapy and cisplatin: Effects on human ovarian cancer ex vivo

Background: Patients with ovarian cancer that is clinically resistant to ci splatin-based chemotherapy have little hope of a cure of their disease. Pho toimmunotherapy, which involves the antibody-targeted delivery of a nontoxi c photosensitizer that is activated to a cytotoxic state with visible light , may offer a new treatment option. Photoimmunotherapy may be applied intra peritoneally to target disseminated tumor, We tested the hypothesis that th is treatment in combination with cisplatin potentiates cytotoxicity in ovar ian cancer cell lines and primary cultures of human tumors. Methods: Five h uman cancer cell lines (ovarian and breast) and 19 primary cultures were st udied. The primary cultures were from solid and ascites tumor samples obtai ned from 14 patients with ovarian cancer who were undergoing primary surger y. The photosensitizer chlorin e(6) was conjugated to the F(ab')(2) fragmen t of the murine monoclonal antibody OC-125, which is directed against the a ntigen CA 125, Cytotoxicity was measured by the microculture tetrazolium as say. Treatments consisted of cisplatin alone, photoimmunotherapy alone, and photoimmunotherapy followed by cisplatin. The fractional product method wa s used to assess synergy in treatment effects. Ex vivo cultured human cells exhibiting 80% or greater survival at cisplatin concentrations of 10 mu M for 24 hours were defined as cisplatin resistant for this study, Results: W hen all cell types (cisplatin sensitive and cisplatin resistant) were consi dered together, combination treatment yielded cytotoxicity that was, on ave rage, 6.9 times (95% confidence interval = 1.86-11.94) greater than that of cisplatin alone (two-sided P =.023). Cisplatin-resistant cells showed a sy nergistic effect of the two treatments (two-sided P = .044), while cisplati n-sensitive cells showed an additive effect. Conclusion: These ex vivo data suggest that platinum resistance in human ovarian cancer cells may be reve rsible by pretreatment with OC-125-targeted photoimmunotherapy, Further stu dies are required to confirm the efficacy of this approach in vivo.