Human immune response to anti-carcinoembryonic antigen murine monoclonal antibodies

We previously demonstrated that patients with carcinoembryonic antigen [CEA]-producing neoplastic tumors, treated with murine monoclonal antibody to CEA, produced antibodies directed against the constant regions [human anti-mouse antibody (HAMA)] and the idiotypes [anti-Id] of these murine immunoglobulins. In this study, we describe a method for analyzing the presence of such antibodies in the sera of these patients. The HAMAs were measured by enzyme immunoassay and removed by immunoadsorption on Affi-Gel mouse IgG. The unabsorbed fraction contained the anti-Id antibodies; their presence was demonstrated by binding to the CEA monoclonal antibody (Ab1). The specificity of the binding was assessed by preincubating the sera with Ab1 and measuring the residual nonspecific binding. When specific binding was detected, the anti-Id antibodies were isolated by adsorption and elution on Affi-Gel Ab1. The anti-Id antibodies were fixed on enzyme immunoassay plates and incubated with a panel of mouse anti-human immunoglobulin to determine their isotypes. In a first series of 24 patients, HAMAs were found in 20 cases and anti-Id antibodies in 19 cases. The isolation of a specific IgG to Ab1 was achieved in 2 cases. In an ongoing series, the HAMA and anti-Id antibodies were detected in all five patients given injections of another monoclonal antibody to CEA. In two patients an IgG1 kappa anti-Id was isolated from the serum. The potential therapeutic effect of these antibodies is under investigation.