Cancer Immunology, Immunotherapy

, Volume 63, Issue 10, pp 1037–1045

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 Fattorossi
  • Alessandra Battaglia
Original Article

DOI: 10.1007/s00262-014-1569-0

Cite this article as:
Buzzonetti, A., Fossati, M., Catzola, V. et al. Cancer Immunol Immunother (2014) 63: 1037. doi:10.1007/s00262-014-1569-0

Abstract

Purpose

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).

Methods

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.

Results

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).

Conclusion

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.

Keywords

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

Abbreviations

Ab3

Anti-anti-idiotypic

Anti-Id

Anti-idiotypic

CTL

Cytotoxic T lymphocytes

ECD

Proprietary name for Texas Red-conjugated phycoerythrin

FITC

Fluorescein

HAMA

Human antimouse antibody

IFN

Interferon

mAb

Monoclonal antibody

MIATA

Minimal information about T cell assays

MIMOSA

Monoclonal antibody immunotherapy for malignancies of the ovary by subcutaneous abagovomab

OC

Ovarian cancer

PE

Phycoerythrin

PeCy5

Cy5-conjugated phycoerythrin

PMT

Photomultiplier tube

RFS

Relapse free survival

SEB

Staphylococcal Enterotoxin B

Supplementary material

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

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
  • Alessandra Battaglia
    • 1
  1. 1.Laboratory of Immunology, Department of Obstetrics and GynaecologyUniversità Cattolica Sacro CuoreRomeItaly