Cancer Immunology, Immunotherapy

, Volume 63, Issue 10, pp 1037–1045 | Cite as

Immunological response induced by abagovomab as a maintenance therapy in patients with epithelial ovarian cancer: relationship with survival—a substudy of the MIMOSA trial

  • Alexia Buzzonetti
  • Marco Fossati
  • Valentina Catzola
  • Giovanni Scambia
  • Andrea FattorossiEmail author
  • Alessandra Battaglia
Original Article



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.


Ovarian cancer vaccine CA125-specific cytotoxic T lymphocytes HAMA Ab3 MIMOSA trial 







Cytotoxic T lymphocytes


Proprietary name for Texas Red-conjugated phycoerythrin




Human antimouse antibody




Monoclonal antibody


Minimal information about T cell assays


Monoclonal antibody immunotherapy for malignancies of the ovary by subcutaneous abagovomab


Ovarian cancer




Cy5-conjugated phycoerythrin


Photomultiplier tube


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.

Supplementary material

262_2014_1569_MOESM1_ESM.pdf (4.2 mb)
Supplementary material 1 (PDF 4 kb)


  1. 1.
    Gupta D, Lis CG (2009) Role of CA125 in predicting ovarian cancer survival—a review of the epidemiological literature. J Ovarian Res 2:13. doi: 10.1186/1757-2215-2-13 PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Legge F, Paglia A, D’Asta M, Fuoco G, Scambia G, Ferrandina G (2011) Phase II study of the combination carboplatin plus celecoxib in heavily pre-treated recurrent ovarian cancer patients. BMC Cancer 11:214. doi: 10.1186/1471-2407-11-214 PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Cannistra SA (2004) Cancer of the ovary. N Engl J Med 351:2519–2529PubMedCrossRefGoogle Scholar
  4. 4.
    Ziebarth AJ, Landen CN, Alvarez RD (2012) Molecular/genetic therapies in ovarian cancer: future opportunities and challenges. Clin Obstet Gynecol 55:156–172PubMedCrossRefGoogle Scholar
  5. 5.
    Miyake TM, Sood AK, Coleman RL (2013) Contemporary use of Bevacizumab in ovarian cancer. Exp Opin Biol Ther 13:283–294CrossRefGoogle Scholar
  6. 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
  7. 7.
    Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348:203–213PubMedCrossRefGoogle Scholar
  8. 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
  9. 9.
    Baum RP, Noujaim AA, Nanci A, Moebus V, Hertel A, Niesen A, Donnerstag B, Sykes T, Boniface G, Hör G (1993) Clinical course of ovarian cancer patients under repeated stimulation of HAMA using MAb OC125 and B43.13. Hybridoma 12:583–589PubMedCrossRefGoogle Scholar
  10. 10.
    Möbus VJ, Baum RP, Bolle M, Kreienberg R, Noujaim AA, Schultes BC, Nicodemus CF (2003) Immune responses to murine monoclonal antibody-B43.13 correlate with prolonged survival of women with recurrent ovarian cancer. Am J Obstet Gynecol 189:28–36PubMedCrossRefGoogle Scholar
  11. 11.
    Gordon AN, Schultes BC, Gallion H, Edwards R, Whiteside TL, Cermak JM, Nicodemus CF (2004) CA125- and tumor-specific T-cell responses correlate with prolonged survival in oregovomab-treated recurrent ovarian cancer patients. Gynecol Oncol 94:340–351PubMedCrossRefGoogle Scholar
  12. 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. 13.
    Jerne NK (1974) Towards a network theory of the immune system. Ann immunol 125C(1–2):373–389Google Scholar
  14. 14.
    Gómez RE, Ardigo ML (2012) Anti-idiotype antibodies in cancer treatment: the pharmaceutical industry perspective. Front Oncol 2:147. doi: 10.3389/fonc.2012.00147 PubMedPubMedCentralGoogle Scholar
  15. 15.
    Schlebusch H, Wagner U, Grünn U, Schultes BA (1995) Monoclonal antiidiotypic antibody ACA 125 mimicking the tumor-associated antigen CA 125 for immunotherapy of ovarian cancer. Hybridoma 14:167–174PubMedCrossRefGoogle Scholar
  16. 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. 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. 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. 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
  20. 20.
    Waldrop SL, Davis KA, Maino VC, Picker LJ (1998) Normal human CD4+ memory T cells display broad heterogeneity in their activation threshold for cytokine synthesis. J Immunol 161:5284–5295PubMedGoogle Scholar
  21. 21.
    Fattorossi A, Battaglia A, Ferrandina G, Coronetta F, Legge F, Salutari V, Scambia G (2004) Neoadjuvant therapy changes the lymphocyte composition of tumor-draining lymph nodes in cervical carcinoma. Cancer 100:1418–1428PubMedCrossRefGoogle Scholar
  22. 22.
    Campoli M, Ferris R, Ferrone S, Wang X (2010) Immunotherapy of malignant disease with tumor antigen (TA)- specific monoclonal antibodies: does its therapeutic efficacy require cooperation with TA-specific CTL? Clin Cancer Res 16:11–20PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Alexia Buzzonetti
    • 1
  • Marco Fossati
    • 1
  • Valentina Catzola
    • 1
  • Giovanni Scambia
    • 1
  • Andrea Fattorossi
    • 1
    Email author
  • Alessandra Battaglia
    • 1
  1. 1.Laboratory of Immunology, Department of Obstetrics and GynaecologyUniversità Cattolica Sacro CuoreRomeItaly

Personalised recommendations