Idiotype vaccination post-bone marrow transplantation for B-cell lymphoma: initial studies in a murine model

Studies in the 38C13 model, a lethal murine B-cell lymphoma of C3H origin, have previously demonstrated the efficacy of immunization with tumor idiotype against established tumors, especially in the setting of reduced tumor burden when combined with chemotherapy. We have extended these studies to test the protective effect of immunization with 38C13 idiotype protein (38C-Id), coupled to KLH and administered with an adjuvant, against a subsequent tumor challenge following lethal total body irradiation (950 R) and reconstitution with syngeneic bone marrow (20 x 10(6) cells) from normal donors. Animals prepared in this manner which were immunized with 38C-Id after 3 weeks recuperation and challenged with 1000 38C13 tumor cells 2 weeks later demonstrated significantly longer survival when compared to control animals which had been immunized with irrelevant idiotype protein. Irradiated reconstituted mice immunized after 5 weeks recuperation and challenged with 1000 tumor cells also demonstrated prolonged survival compared to controls, as well as a small number of cures (approximately 40%). Anti-38C-Id antibodies, implicated in the mechanism of idiotype induced anti-tumor immunity in this model, were detectable after immunization at both 3 and 5 weeks, although there was no significant correlation between serum antibody levels and survival of individual mice. These results suggest that immunologic recovery as early as 3 to 5 weeks following marrow grafting is sufficient to allow induction of idiotype-specific, anti-tumor immunity and form a model for our clinical trial of tumor idiotype vaccination for patients with B-cell lymphoma undergoing autologous BMT.