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Biotech / Medical : Pharmacyclics (PCYC) -- Ignore unavailable to you. Want to Upgrade?

To: RWReeves who wrote (531)	9/15/1999 11:01:00 AM
From: Biomaven	Read Replies (1) \| Respond to of 717

Although this isn't PCYC work it is somewhat related - it's maybe a sign that a combo with LuTex and chemo might be effective. Note that PCYC has been muttering about a Gd-Tex and chemo combo for a while now. Of course the PCYC drugs don't need no antibodies to end up at the right spot, although the mechanism whereby this happens still isn't very clear (at least to me). Journal of the National Cancer Institute, Vol. 91, No. 18, 1557-1563, September 15, 1999 © 1999 Oxford University Press -------------------------------------------------------------------- REPORTS Combination Photoimmunotherapy and Cisplatin: Effects on Human Ovarian Cancer Ex Vivo Linda R. Duska, Michael R. Hamblin, Jaimie L. Miller, Tayyaba Hasan Affiliations of authors: L. R. Duska, Wellman Laboratories of Photomedicine and Vincent Memorial Obstetrics and Gynecology Service, Harvard Medical School, Massachusetts General Hospital, Boston; M. R. Hamblin, J. L. Miller, T. Hasan, Department of Dermatology, Wellman Laboratories of Photomedicine, Harvard Medical School, Massachusetts General Hospital. Correspondence to: Tayyaba Hasan, Ph.D., Department of Dermatology, Wellman Laboratories of Photomedicine, Harvard Medical School, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114 (e-mail: hasan@helix.harvard.mgh.edu). BACKGROUND: Patients with ovarian cancer that is clinically resistant to cisplatin-based chemotherapy have little hope of a cure of their disease. Photoimmunotherapy, which involves the antibody-targeted delivery of a nontoxic photosensitizer that is activated to a cytotoxic state with visible light, may offer a new treatment option. Photoimmunotherapy may be applied intraperitoneally to target disseminated tumor. We tested the hypothesis that this treatment in combination with cisplatin potentiates cytotoxicity in ovarian cancer cell lines and primary cultures of human tumors. METHODS: Five human cancer cell lines (ovarian and breast) and 19 primary cultures were studied. The primary cultures were from solid and ascites tumor samples obtained from 14 patients with ovarian cancer who were undergoing primary surgery. The photosensitizer chlorin e6 was conjugated to the F(ab')2 fragment of the murine monoclonal antibody OC-125, which is directed against the antigen CA 125. Cytotoxicity was measured by the microculture tetrazolium assay. Treatments consisted of cisplatin alone, photoimmunotherapy alone, and photoimmunotherapy followed by cisplatin. The fractional product method was used to assess synergy in treatment effects. Ex vivo cultured human cells exhibiting 80% or greater survival at cisplatin concentrations of 10 µM for 24 hours were defined as cisplatin resistant for this study. RESULTS: When all cell types (cisplatin sensitive and cisplatin resistant) were considered together, combination treatment yielded cytotoxicity that was, on average, 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 synergistic effect of the two treatments (two-sided P = .044), while cisplatin-sensitive cells showed an additive effect. CONCLUSION: These ex vivo data suggest that platinum resistance in human ovarian cancer cells may be reversible by pretreatment with OC-125-targeted photoimmunotherapy. Further studies are required to confirm the efficacy of this approach in vivo. On a different topic, I note that the Gd-Tex (Xcytrin) Phase III now has 30 sites open, including some in Canada, France and the Netherlands. Peter