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Immune responses to murine monoclonal antibody-B43.13 correlate with prolonged survival of women with recurrent ovarian cancer

2003; Elsevier BV; Volume: 189; Issue: 1 Linguagem: Inglês

10.1067/mob.2003.347

1097-6868

Volker Möbus, Richard P. Baum, Marcus Bolle, R. Kreienberg, A.A. Noujaim, Birgit C. Schultes, Christopher F. Nicodemus,

Toxin Mechanisms and Immunotoxins

We evaluated the therapeutic efficiency of the murine monoclonal antibody-B43.13 in the treatment of patients with recurrent ovarian cancer.This was a retrospective study of immune responses and survival in 44 patients who were treated with technetium 99m-labeled monoclonal antibody-B43.13, a murine monoclonal antibody that is directed against the tumor-associated antigen CA125. Most patients were pretreated heavily. Biologic activity was quantified by the assay of immune responses to the human anti-murine antibodies against the monoclonal antibody-B43.13 variable region (Ab(2)) and antibodies that target the CA 125 antigen itself (anti-CA 125 antibody).More than one half of patients (56.8%) survived for >12 months after the first dose of monoclonal antibody B43.13; 34.1% of the patients survived >24 months. To date, 6 of the 44 patients are alive, with survival times of 4 to 7.5 years after the start of the antibody treatment. More than 60% of the evaluable patients met predefined criteria for robust, treatment-emergent human anti-murine antibodies and Ab(2) responses, and these responses were associated with improved survival rates. Median survival time increased approximately 3-fold for human anti-murine antibody responders (22.6 months) versus nonresponders (7.2 months; P <.0016, log-rank test) and 2-fold for Ab(2) responders (18.3 months) versus nonresponders (9.3 months). No serious drug-associated adverse events were reported.The associations between multiple types of immune response and improved clinical outcomes suggest that monoclonal antibody-B43.13 should be further evaluated for potential use as an immunotherapy for CA125-expressing malignancies.