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

Silvia Miotti, Donatella R M Negri, Olga Valota, Marcella Calabrese, Reinder L H Bolhuis, Jan W. Gratama, Maria I. Colnaghi, Silvana Canevari

Research output: Contribution to journalArticle

Abstract

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 (≥ 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 16116 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 HANA levels. The long-lasting HAMA response maintained an anti-idiotypic component, directed mainly against the αCD3 idiotype of bi-MAb OC/TR in 2 out of 3 cases tested.

Original languageEnglish
Pages (from-to)62-68
Number of pages7
JournalInternational Journal of Cancer
Volume84
Issue number1
DOIs
Publication statusPublished - 1999

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Antibody Formation
Anti-Idiotypic Antibodies
Carcinoma
Survival
T-Lymphocytes
Serum
Monoclonal Antibodies
OC-TR monoclonal antibody
Ovarian Neoplasms
Immunotherapy
Radioimmunoassay
Appointments and Schedules
Antigens
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Level of anti-mouse-antibody response induced by bi-specific monoclonal antibody OC/TR in ovarian-carcinoma patients is associated with longer survival. / Miotti, Silvia; Negri, Donatella R M; Valota, Olga; Calabrese, Marcella; Bolhuis, Reinder L H; Gratama, Jan W.; Colnaghi, Maria I.; Canevari, Silvana.

In: International Journal of Cancer, Vol. 84, No. 1, 1999, p. 62-68.

Research output: Contribution to journalArticle

Miotti, Silvia ; Negri, Donatella R M ; Valota, Olga ; Calabrese, Marcella ; Bolhuis, Reinder L H ; Gratama, Jan W. ; Colnaghi, Maria I. ; Canevari, Silvana. / Level of anti-mouse-antibody response induced by bi-specific monoclonal antibody OC/TR in ovarian-carcinoma patients is associated with longer survival. In: International Journal of Cancer. 1999 ; Vol. 84, No. 1. pp. 62-68.
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