Characterization of human IgG antimouse antibody in patients with B-cell malignancies

Gerald L Denardo, Gary R. Mirick, Linda A. Kroger, Bonnie M. Bradt, Kathleen R. Lamborn, Sally J. DeNardo

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11 Scopus citations

Abstract

Purpose: Immunotherapeutic approaches to cancer offer an attractive adjunct to conventional modalities, although human antiglobulin responses can be an obstacle to repeated treatment. This study of a large number of patients with B-cell malignancies, over an extended period of time, characterized their human antimouse antibody (HAMA) seroconversion. Experimental Design: A total of 617 samples from 112 subjects were analyzed for HAMA titers. Eighty-five patients with B-cell malignancies; 12 breast cancer patients, and 15 volunteers were titered for comparison. Fifty-six B-cell malignancy patients were titered for HAMA throughout Lym-1 radioimmunotherapy (RIT); 29 were titered after a single imaging dose of Lym-1 antibody. Results: Baseline titers did not correlate with subsequent HAMA seroconversion against Lym-1. Only 1 of 29 (3%) of the patients developed HAMA after an imaging dose of Lym-1. Of the RIT trial group, 37 of 56 (66%) never developed HAMA above baseline despite multiple doses. Of those who did (19 of 56; or 34%), the HAMA responses fell into two categories. Thirteen responded rapidly (median of 31 days) and were termed "early responders," whereas 6, termed "late responders," had a median response time of 111 days. Early responders developed higher peak HAMA titers with fewer exposures to Lym-1 and took longer to return to baseline than did the late responders. The frequency of new antiglobulin seroconversion decreased as the number of exposures increased. Conclusions: Seventy-seven percent of B-cell malignancy patients developed no response or a weak response after multiple doses of mouse Lym-1 antibody. Positive responders occurred in all histology types and fell into two categories differing in seroconversion time and titer, possibly indicative of the initial state of the immune system.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume9
Issue number10 II
StatePublished - Oct 1 2003

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Denardo, G. L., Mirick, G. R., Kroger, L. A., Bradt, B. M., Lamborn, K. R., & DeNardo, S. J. (2003). Characterization of human IgG antimouse antibody in patients with B-cell malignancies. Clinical Cancer Research, 9(10 II).