The human antimouse immunoglobulin response and the anti-idiotypic networkhave no influence on clinical outcome in patients with minimal residual colorectal cancer treated with monoclonal antibody CO17-1A

Murine monoclonal antibodies (mAbs), when administered to patients, induce a human antimouse immunoglobulin immune response, especially when multiple infusions are required to obtain therapeutic efficacy. In a randomized Phas e II clinical study, 83 patients with colorectal carcinoma of stage Dukes C were treated with the murine IgG2a mAb 17-1A (ab1) after curative surgery. The regimen consisted of a single infusion of 500mg of 17-1A within 2 week s after surgery, followed by 100mg of mAbs four times every 4 weeks. Sera w ere taken every 2-3 weeks and screened for human antimouse antibodies (HAMA ), HAMA were measured by a capture ELISA and an indirect antihuman immunogl obulin ELISA for the analysis of IgG and IgM isotypes, Anti-idiotypic antib odies (ab2) were detected by an inhibition ELISA, and anti-anti-idiotypic a ntibodies (ab3), recognizing the original antigen, were determined by flow cytometric analysis. About 20% of patients failed to develop HAMA; in the o ther patients, antibody titers were initially low after the first two infus ions and reached their maximum only after a fifth infusion at 18-20 weeks a fter surgery, An analysis that differentiated between patients who develope d recurrences and those who remained tumor-free did not show any difference in antibody titers between the two groups, neither for total HAMA nor for IgG, IgM, or ab2, The formation of ab3 was analyzed in eight patients and p roved to be negative in all of them. HAMA remained detectable up to 2 years after the last treatment. In patients who experienced adverse events assoc iated with therapy, HAMA titers tended to rise earlier; this difference, ho wever, was not statistically significant. Thus, neither a beneficial nor a detrimental effect of HAMA formation could be determined for the clinical r esponse to antibody therapy.