Bispecific antibody targeted T cell therapy of ovarian cancer: Clinical results and future directions

S. Canevari, D. Mezzanzanica, A. Mazzoni, D. R M Negri, V. Ramakrishna, R. L H Bolhuis, M. I. Colnaghi, G. Bolis

Research output: Contribution to journalArticle

Abstract

The high frequency of relapse after induction chemotherapy in advanced ovarian carcinoma patients calls for new therapeutic modalities. Retargeted T cell-mediated lysis can be achieved using the bispecific antibody (BsmAb) OCTR, directed to CD3 on T cells and to the folate receptor on ovarian carcinoma cells. Twenty-eight patients with limited intraperitoneal disease after first-line therapy entered a phase II study. They received two i.p. 5 day cycles of activated PBMC retargeted with OCTR. Despite unfavorable tumor characteristics, 7 of 26 patients (27 %) showed complete or partial intraperitoneal responses with strict surgicopathologic evaluation. In most cases, the disease relapsed outside the peritoneal cavity, and in 1 case complete intraperitoneal response was accompanied by progression in retroperitoneal lymph nodes. The morbidity was mild to moderate and transient. Combination of i.v. and i.p. administration of OCTR-retargeted lymphocytes will possibly lead to extraperitoneal cure. Ongoing clinical studies indicate that the i.v. infusion of up to 8 x 108 OCTR-retargeted T lymphocytes does not induce a higher toxicity than the i.p. treatment. To avoid PBMC preactivation, new approaches for delivering accessory signals are under investigation. Preliminary results indicate that nonactivated PBMC retargeted by OCTR in the presence of an anti-CD28 monoclonal antibody (mAb) are able to significantly inhibit tumor growth.

Original languageEnglish
Pages (from-to)423-427
Number of pages5
JournalJournal of Hematotherapy
Volume4
Issue number5
Publication statusPublished - 1995

ASJC Scopus subject areas

  • Immunology
  • Hematology

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    Canevari, S., Mezzanzanica, D., Mazzoni, A., Negri, D. R. M., Ramakrishna, V., Bolhuis, R. L. H., Colnaghi, M. I., & Bolis, G. (1995). Bispecific antibody targeted T cell therapy of ovarian cancer: Clinical results and future directions. Journal of Hematotherapy, 4(5), 423-427.