Combined syngeneic bone marrow transplantation and immunotherapy of a murine B-cell lymphoma: active immunization with tumor-derived idiotypic immunoglobulin.

Overview

Recurrence of the underlying malignancy remains a major cause of treatment failure after autologous bone marrow transplantation (BMT) for patients with lymphoma. In this regard, we have developed an immunotherapeutic approach designed to induce resistance against residual tumor cells persisting after BMT. Previous studies in the model system of 38C13, a lethal B-cell lymphoma of C3H origin, have shown that active immunization with purified tumor-derived surface immunoglobulin (Id), as a tumor-associated antigen, produces resistance to tumor growth. Id immunization of lethally irradiated mice at 3 or 5 weeks after reconstitution with syngeneic bone marrow resulted in significantly prolonged survival after tumor challenge compared with nonspecifically immunized controls. Low levels of idiotype-specific antibody were also demonstrated in the sera of specifically immunized mice at this early time, when other functional studies in the literature of immunocompetence after syngeneic reconstitution might have predicted incomplete recovery. Immunization of mice before lethal irradiation and syngeneic marrow reconstitution also induced significant resistance to tumor challenge, suggesting the persistence of established host antitumor immunity through total body irradiation. These studies demonstrate the feasibility of id immunization in conjunction with bone marrow transplantation.