Effect of immunosuppressive agents on the immunogenicity and efficacy of an immunotoxin in mice

Elysa E. Gelber, Ellen S. Vitetta

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Immunotoxins (ITs) are potent cytotoxic agents used in the treatment of cancer, autoimmune disease, and graft-versus-host disease. Results from clinical trials demonstrate that many IT-treated patients, especially those with an intact immune system, develop anti-IT antibodies that may prohibit repeated IT dosing. We, therefore, evaluated a panel of novel immunosuppressive (IS) agents for their ability to inhibit the antitoxin immune response in mice receiving multiple courses of a ricin A chain (RTA)- containing IT and also assessed whether this suppression would result in an increase in IT-mediated antitumor activity. The results indicate that a 3- day pretreatment, plus one additional boost 2 weeks later, of a combination of hCTLA4Ig + anti-CD40L, virtually eliminated the anti-RTA response in normal mice receiving six weekly injections of an IT. When tested in BCL1 tumor-bearing mice, the concomitant use of a combination of hCTLA4Ig + anti- CD40L and six doses of the IT resulted in a 1.5-fold increase in tumor cell killing, as compared with treatment with IT alone. We conclude that a combination of IS + IT therapy should facilitate the administration of multiple courses of IT, as well as enhance its antitumor activity.

Original languageEnglish (US)
Pages (from-to)1297-1304
Number of pages8
JournalClinical Cancer Research
Volume4
Issue number5
StatePublished - May 1 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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