ACTIVE IMMUNIZATION OF MURINE ALLOGENEIC BONE-MARROW TRANSPLANT DONORS WITH B-CELL TUMOR-DERIVED IDIOTYPE - A STRATEGY FOR ENHANCING THE SPECIFIC ANTITUMOR EFFECT OF MARROW GRAFTS

Persistence of the underlying malignancy remains the major obstacle li miting the success of high-dose chemoradiotherapy with allogeneic bone marrow transplantation (BMT) for lymphomas and multiple myeloma, We u sed the C3H 38C13 murine B-cell lymphoma, which expresses and secretes clonally derived Ig, the idiotype of which can serve as a tumor-speci fic antigen, to test the principle of transfer of tumor idiotype-speci fic immunity with BM. BALB/c marrow donors were twice immunized with 3 8C13-derived Ig, or with an isotype-matched control Ig, conjugated to keyhole limpet hemocyanin. Lethally irradiated C3H recipients reconsti tuted with marrow from idiotype immune, but not nonspecifically immune , donors demonstrated protection against subsequent lethal tumor chall enge. The immunoprotective effect of immune allogeneic marrow was abro gated by T-cell depletion of the marrow graft before infusion, Low lev els of serum anti-idiotypic antibody remained unaltered in recipients of T-cell-depleted immune marrow, consistent with a primary role for T -cell immunity in the cellular mechanism of this phenomenon. A modest therapeutic effect of immune allogeneic marrow was observed against 10 day, 1 cm established subcutaneous tumors, but only in combination wi th a booster immunization of the recipient post-BMT. These results pro vide the rationale for a novel strategy for enhancing the specific ant itumor effect of allogeneic marrow grafts.