Human anti-murine immunoglobulin responses in patients receiving monoclonal antibody therapy.

Human anti-murine immunoglobulin responses were assessed in serum from three groups of patients receiving murine monoclonal antibody therapy. Each of the three patient groups responded differently. Chronic lymphocytic leukemia patients demonstrated little or no preexisting murine immunoglobulin G-reactive antiglobulin prior to treatment, while the cutaneous T-cell lymphoma and melanoma patients demonstrated preexisting antiglobulin levels in the same range as those demonstrated in healthy controls. None of 11 chronic lymphocytic leukemia patients receiving the T101 monoclonal antibody demonstrated an antiglobulin response, whereas all four of the cutaneous T-cell lymphoma patients receiving the same antibody developed increased levels of antiglobulins. Three of nine malignant melanoma patients receiving the 9.2.27 monoclonal antibody showed an increase in antiglobulin titers. In patients developing antiglobulin responses, the response was rapid, typically being detectable within 2 weeks. The antiglobulins were primarily immunoglobulin G and, with the exception of a single melanoma patient in whom the response appeared to have a substantial 9.2.27-specific component (i.e., antiidiotype), were cross-reactive with most murine immunoglobulin G preparations tested. This pattern of results suggested that the antiglobulin was a secondary immune reaction with elevation of the levels of preexisting antiglobulin which was cross-reactive with the mouse antibody administered. While the presence of serum antiglobulin would be expected to present major complications to monoclonal antibody therapy, no clinical toxicity related to antiglobulin responses was observed in these patients, and no inhibition of antibody localization on tumor cells was seen.