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
Lw. Kwak et al., 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, Blood, 87(7), 1996, pp. 3053-3060
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.