Mechanism of B cell lymphoma immunotherapy with passive xenogeneic anti-idiotype serum.

Abstract

Abstract Previously, we have reported that xenogeneic antiidiotype serum can successfully eliminate growth of the CHI murine B cell lymphoma in vivo. In this study, various factors that influence the success of passive antiidiotype serum therapy were examined. Anti-idiotype serum therapy was dependent on tumor dose and was tumor specific in vivo. The curative capacity of the antiidiotype serum was found in the IgG fraction; however, (Fab′)2 fragments of the IgG were totally ineffective as an immunotherapeutic agent. The role of several host factors in the mechanism of therapy was also investigated. Studies with genetically C5-deficient mice and cobra venom factor-treated mice unequivocally demonstrated that the pasive anti-idiotype serum immunotherapy does not involve C-mediated tumor lysis in vivo. Similarly, splenectomy, thymectomy, sublethal irradiation, and treatment with cyclophosphamide did not abrogate the effectiveness of anti-idiotype serum therapy. Treatment with anti-I-Jk antiserum to deplete T suppressor cells also did not prevent the therapeutic effect of the antiserum. Although host lymphocytes and complement do not seem to be involved in the mechanism of therapy, evidence is presented to demonstrate that a host component, which matures at 6 wk of age and declines in activity in old mice, is required for successful serotherapy. Based on these data, passive anti-idiotype serum immunotherapy appears to depend on the Fc portion of the anti-idiotype antibody and on the presence of presumably Fc receptor-bearing host cells.