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ANTI-CHELATE ANTIBODIES AFTER INTRAPERITONEAL YTTRIUM-90-LABELED MONOCLONAL-ANTIBODY IMMUNOCONJUGATES FOR OVARIAN-CANCER THERAPY
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Abstract
En 中文
The development of stable chelating agents for metal isotopes (e.g., Y-90) such as CITC-DTPA, a benzyl-analog of DTPA, allowed us to evaluate the efficacy of Y-90-labeled HMFG1 MAb administered intraperitoneally in patients with ovarian cancer. Our previous studies of Y-90-HMFG1 antibody, however, showed that all patients developed anti-chelate antibody responses (to the macrocycle benzyl-DOTA), resulting in clinical side effects in a significant percentage of this group. Methods: We evaluated the immunogenicity of CITC-DTPA (administered to 12 patients as Y-90-HMFG1-CITC-DTPA after coupling it to HSA using solid-phase ELISA. Results: Eleven of 12 evaluable patients developed anti-CITC-DTPA antibodies. Five patients (similar to 40%) developed hypersensitivity syndrome, most likely due to a type III immune reaction (serum sickness). Most patients had a low titer of pre-existing anti-chelate response which correlated positively with post-therapy response levels (p=0.001). IgM anti-CITC-DTPA antibodies developed 2 wk while IgG antibodies developed 3 wk after treatment. Western blot analysis of post-therapy sera revealed a reaction with HSA-CITC-DTPA (60 kDa band) and no reaction with HSA or HSA-DTPA, whereas pre-therapy sera of the same patients were negative to all antigens. Conclusion: CITC-DTPA is immunogenic in patients after intraperitoneal administration of Y-90-CITC-DTPA labeled MAbs. Self-limiting clinical side effects consistent with a serum sickness-like immune reaction were observed in 5 of 12 patients.
Keywords:
MONOCLONAL ANTIBODIES
RADIOIMMUNOTHERAPY
CHELATES
Y-90
OVARIAN CANCER
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