Level of anti-mouse-antibody response induced by bi-specific monoclonal antibody OC/TR in ovarian-carcinoma patients is associated with longer survival

Int J Cancer. 1999 Feb 19;84(1):62-8. doi: 10.1002/(sici)1097-0215(19990219)84:1<62::aid-ijc12>3.0.co;2-t.


More than 60% of cancer patients injected with intact murine monoclonal antibody (MAb) develop a humoral response against the antigen even after a single dose. Analysis of a series of 35 ovarian-cancer patients entered in phase-I and -II clinical studies of T-cells retargeted with the bi-specific F(ab')2 OC/TR revealed: (i) a detectable human anti-mouse antibody (HAMA) response in 31/35 (88%) patients, with high HAMA levels (> or = 150 ng/ml) in 18/31 (58%) cases by the end of the treatment; (ii) no correlation between HAMA levels and the form of delivery of the mAb (OC/TR bound to T cells or bound plus soluble), time schedule or cumulative dose; (iii) an association between high HAMA levels and favorable clinical parameters and response to immunotherapy; and (iv) a significantly longer median survival probability in patients with high HAMA levels than in patients with lower HAMA levels, even when the sub-group of non-responder patients was considered. Evaluation of the anti-idiotypic response in HAMA-positive sera indicated that 11/17 sera showed high-titer (>6000) binding of OC/TR, as evaluated by a specific radioimmunoassay, and 15/18 and 16/16 sera specifically inhibited the binding of the MOv18 and anti-CD3 parental MAbs to ovarian-carcinoma cells and T lymphocytes respectively. Of 7 patients evaluated for duration of the HAMA response, 5 showed stable or even increased HAMA levels. The long-lasting HAMA response maintained an anti-idiotypic component, directed mainly against the alphaCD3 idiotype of bi-MAb OC/TR in 2 out of 3 cases tested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / biosynthesis
  • Antibodies, Anti-Idiotypic / immunology*
  • Antibodies, Bispecific / immunology
  • Antibodies, Bispecific / therapeutic use*
  • Antibodies, Heterophile / immunology
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Biomarkers
  • Female
  • Humans
  • Mice
  • Neoplasm Staging
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / therapy*
  • Prognosis
  • Survival Rate
  • T-Lymphocytes / immunology
  • Time Factors


  • Antibodies, Anti-Idiotypic
  • Antibodies, Bispecific
  • Antibodies, Heterophile
  • Antibodies, Monoclonal
  • Biomarkers
  • OC-TR monoclonal antibody