Immunological response induced by abagovomab as a maintenance therapy in patients with epithelial ovarian cancer: relationship with survival—a substudy of the MIMOSA trial
- 267 Downloads
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
HAMA and Ab3 data were provided by Menarini Ricerche, Pomezia, Italy.
Conflict of interest
Part of reagents (e.g., mAbs, CA125, staining buffers, etc.) and disposables (plasticwares) have been provided by Menarini Ricerche, Pomezia, Italy. The authors declare they have no financial or other interest that is relevant to the subject matter under consideration in this article with Menarini Ricerche.
- 6.Liu JF, Konstantinopoulos PA, Matulonis UA (2014) PARP inhibitors in ovarian cancer: Current status and future promise. Gynecol Oncol. doi: 10.1016/j.ygyno.2014.02.039
- 8.Berek JS, Taylor PT, Gordon A, Cunningham MJ, Finkler N, Orr J Jr, Rivkin S, Schultes BC, Whiteside TL, Nicodemus CF (2004) Randomized, placebo-controlled study of oregovomab for consolidation of clinical remission in patients with advanced ovarian cancer. J Clin Oncol 22:3507–3516PubMedCrossRefGoogle Scholar
- 12.Braly P, Nicodemus CF, Chu C, Collins Y, Edwards R, Gordon A, McGuire W, Schoonmaker C, Whiteside T, Smith LM, Method M (2009) The Immune adjuvant properties of front-line carboplatin-paclitaxel: a randomized phase 2 study of alternative schedules of intravenous oregovomab chemoimmunotherapy in advanced ovarian cancer. J Immunother 32:54–65PubMedCrossRefGoogle Scholar
- 13.Jerne NK (1974) Towards a network theory of the immune system. Ann immunol 125C(1–2):373–389Google Scholar
- 16.Reinartz S, Köhler S, Schlebusch H, Krista K, Giffels P, Renke K, Huober J, Möbus V, Kreienberg R, DuBois A, Sabbatini P, Wagner U (2004) Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II). Clin Cancer Res 10:1580–1587PubMedCrossRefGoogle Scholar
- 17.Pfisterer J, du Bois A, Sehouli J, Loibl S, Reinartz S, Reuss A, Canzler U, Belau A, Jackisch C, Kimmig R, Wollschlaeger K, Heilmann V, Hilpert F (2006) The anti-idiotypic antibody abagovomab in patients with recurrent ovarian cancer. A phase I trial of the AGO-OVAR. Ann Oncol 17:1568–1577PubMedCrossRefGoogle Scholar
- 18.Sabbatini P, Dupont J, Aghajanian C, Derosa F, Poynor E, Anderson S, Hensley M, Livingston P, Iasonos A, Spriggs D, McGuire W, Reinartz S, Schneider S, Grande C, Lele S, Rodabaugh K, Kepner J, Ferrone S, Odunsi K (2006) Phase I study of abagovomab in patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer. Clin Cancer Res 12:5503–5510PubMedCrossRefGoogle Scholar
- 19.Sabbatini P, Harter P, Scambia G, Sehouli J, Meier W, Wimberger P, Baumann KH, Kurzeder C, Schmalfeldt B, Cibula D, Bidzinski M, Casado A, Martoni A, Colombo N, Holloway RW, Selvaggi L, Li A, del Campo J, Cwiertka K, Pinter T, Vermorken JB, Pujade-Lauraine E, Scartoni S, Bertolotti M, Simonelli C, Capriati A, Maggi CA, Berek JS, Pfisterer J (2013) Abagovomab as maintenance therapy in patients with epithelial ovarian cancer: a Phase III trial of the AGO OVAR, COGI, GINECO, and GEICO—the MIMOSA study. J Clin Oncol 31:1554–1561PubMedCrossRefGoogle Scholar