The role of humoral and cellular immunity in patients developing human anti-murine immunoglobulin antibody responses after radioimmunotherapy.

Epstein-Barr virus (EBV)-immortalised B cell lines were established from patients receiving multiple administrations (two or more) of radiolabelled murine monoclonal antibodies for the treatment of ovarian cancer. Cells secreting anti-id2 Ig, an immunoglobulin with binding specificities comparable to the administered murine monoclonal antibody, were isolated by using magnetic beads coated with tumour-associated antigen, incubated with the cells and concentrated with a magnetic particle concentrator. Cross-linking of the immunoglobulin receptors by the antigen-coated beads appears to stimulate proliferation, resulting in increased secretion of the human anti-tumour-associated antigen antibodies. The T cell responses were studied and it was found that monoclonal antibody therapy appears to lead to an increase in the population of T cells committed to proliferate in response to both specific antigen and non-specific mitogens. Multiple administrations of monoclonal antibody induce the generation of T cells which proliferate in vitro following stimulation with murine antibodies. The relevant (administered) monoclonal antibody induces higher proliferation rates than an idiotypically unrelated antibody of the same isotype, indicating the generation of idiotypically restricted T cell responses in these patients.