Immunological response induced by abagovomab as a maintenance therapy in patients with epithelial ovarian cancer: relationship with survival—a substudy of the MIMOSA trial
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- Buzzonetti, A., Fossati, M., Catzola, V. et al. Cancer Immunol Immunother (2014) 63: 1037. doi:10.1007/s00262-014-1569-0
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To determine whether abagovomab induces protective immune responses in ovarian cancer patients in first clinical remission. The present analysis is a substudy of monoclonal antibody immunotherapy for malignancies of the ovary by subcutaneous abagovomab trial (NCT00418574).
The study included 129 patients, 91 in the abagovomab arm and 38 in the placebo arm. Circulating CA125-specific cytotoxic T lymphocytes (CTL) were measured by a flow cytometry-based interferon-γ producing assay. Human antimouse antibody and anti-anti-idiotypic (Ab3) were assessed by ELISA. Patients were evaluated before starting the treatment and at different time points during induction and maintenance phases.
A similar percentage of patients in both the placebo and abagovomab arms had CA125-specific CTL (26.3 and 31.8 %, respectively; p = 0.673 by Fisher’s exact test). Patients with CA125-specific CTL in both arms tended to have an increased relapse-free survival (RFS, log-rank test p = 0.095) compared to patients without. Patients (n = 27) in the abagovomab arm without CA125-specific CTL but that developed Ab3 above the cutoff (defined as median Ab3 level at week 22) had a prolonged RFS compared to patients (n = 24) that did not develop Ab3 above the cutoff (log-rank test p = 0.019).
Abagovomab does not induce CA125-specific CTL. However, patients with CA125-specific CTL perform better than patients without, irrespective of abagovomab treatment. Abagovomab-induced Ab3 associate with prolonged RFS in patients without CA125-specific CTL. Further studies are needed to confirm these data and to assess the potential utility of these immunological findings as a tool for patient selection in clinical trial.
KeywordsOvarian cancer vaccine CA125-specific cytotoxic T lymphocytes HAMA Ab3 MIMOSA trial
Cytotoxic T lymphocytes
Proprietary name for Texas Red-conjugated phycoerythrin
Human antimouse antibody
Minimal information about T cell assays
Monoclonal antibody immunotherapy for malignancies of the ovary by subcutaneous abagovomab
Relapse free survival
Staphylococcal Enterotoxin B