Human antiglobulin response to foreign antibodies: Therapeutic benefit?

Gerald L Denardo, Bonnie M. Bradt, Gary R. Mirick, Sally J. DeNardo

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Immunotherapies for cancer offer attractive alternatives to conventional therapies although human anti-globulin antibody (HAGA) against the antibody (Ab) administered to the patient can be an obstacle to repeated treatment. Monoclonal antibodies (mAb), whether foreign or human in origin, have been used safely in patients for two decades. Adverse events have not proven to be significant clinical obstacles, although alterations of pharmacokinetic behavior of subsequently administered Ab can lead to less effective therapy. Not only is HAGA safe, but it can be associated with beneficial immunity in patients. Studies have shown that some patients have unexpectedly prolonged survival associated with HAGA. In our own non-Hodgkin's lymphoma (NHL) patients treated with mouse Lym-1 anti-lymphoma mAb, a high human anti-mouse Ab (HAMA) titer was associated with increased survival. The possible mechanisms linking HAMA responses to survival are likely related to Ab generated against the idiotopes of the administered Ab. An induced immune cascade in these patients, including anti-idiotypic Ab (Ab2) and cytotoxic Ab1' or Ab3 probably contributed to survival. In summary, HAGA should not a priori preclude the therapeutic use of Ab for cancer.

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalCancer Immunology, Immunotherapy
Volume52
Issue number5
StatePublished - May 1 2003

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Keywords

  • Antibody
  • Cancer
  • Human anti-mouse antibody
  • Immunotherapy
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Oncology

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