M. Zeis et al., Transfer of idiotypic protein primed allogeneic marrow grafts elicits potent graft-versus-myeloma effects in mice, BONE MAR TR, 27(3), 2001, pp. 279-285
Citations number
28
Categorie Soggetti
Hematology,"Medical Research Diagnosis & Treatment
The active immunization of bone marrow (BM) donors with myeloma immunoglobu
lin (Ig) results in an idiotypic T cell response that can be transferred to
the recipient. Using a murine model we evaluated the effectiveness, side-e
ffects and underlying mechanisms of this approach. Balb/c (H-2(d)) mice wer
e given a dose of HOPC-1F myeloma cells secreting the monoclonal IgG,, foll
owed by lethal total body irradiation (7.5 Gy) 2 days later and a subsequen
t transplantation of 2 x 10(7) allogeneic MHC-matched DBA/2-derived marrow
cells. Donors were pre-immunized with three i.p. injections of HOPCIgG2a Or
control Ig given with incomplete Freund's adjuvants (LFA) spaced 1 week ap
art. In some experiments, donor-spleen cells were additionally transferred
2 h post transplant, Injection of HOPC-myeloma led to death of all animals
after a median survival time (MST) of 42 days, A lethal dose of TBI followe
d by transfer of unmanipulated marrow grafts plus splenocytes resulted in m
oderate antimyeloma effects with 8% of mice achieving long-term survival. N
early the same results were obtained after transplantation of BM immunized
with the control Ig, In contrast, transplantation of marrow grafts from HOP
CIgG2a immunized donors exerted a significant GVM effect with 63% long-term
survival for more than 180 days. The additional transfer of 2 x 107 immune
splenocytes derived from the saline donor resulted in even stronger anti-m
yeloma effects (FFR 87%), No increase in the incidence of severe acute GVHD
was observed. In vitro data suggest that allogeneic CD8(+) idiotype-specif
ic T cells may be the major effector cells. Our results demonstrate that ac
tive immunization of the donor with the myeloma-specific Ig can induce powe
rful graft-versus-myeloma effects after allogeneic BMT,