The unique antigenic determinants (idiotype (Id)) of the immunoglobulin secreted by myeloma tumor can serve as a tumor-specific antigen for active immunotherapy. Our objective was to induce tumor-specific T-cell immunity in bone marrow transplant (BMT) donors to enhance antitumor effects of allografts. We vaccinated five HLA-matched sibling donors with myeloma Id proteins isolated from recipient plasma before bone marrow harvest. Recipients were administered booster Id immunizations following transplantation. Vaccination induced donor Id and carrier-specific cellular and/or humoral immune responses. Two recipients died within 30 days of BMT from transplant-related complications. Id and carrier-specific T-cell responses were detected in all three remaining patients post-, but not pre-BMT and persisted for 18 months. All three surviving patients converted from partial to complete responses following BMT. Two of the three patients remain disease-free 7 years and 8 years after BMT, and the third died of renal failure after 5.5 years while in complete remission from myeloma. Our results suggest that myeloma Id vaccination induces specific T-cell immunity in healthy donors which may be transferable by BMT, is associated with prolonged disease-free survival of recipients, and may represent a general strategy to enhance graft-versus-tumor effect in other malignancies for which defined tumor-specific antigens exist.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.
[Show abstract][Hide abstract] ABSTRACT: Hematopoietic stem cell transplantation (HSCT) is a curative therapy for a variety of hematological malignancies including
acute and chronic leukemia, non-Hodgkin lymphoma, and Hodgkin lymphoma . In addition, better disease control and improved
survival can be achieved in patients with multiple myeloma (MM), though it is presently unclear whether patients can be cured
with HSCT . However, relapse of the underlying malignant disease is still a significant clinical problem. After autologous
HSCT, the relapse rate is as high as 60% while after allogeneic HSCT up to 30% of patients relapse . If relapse occurs,
the prognosis is generally poor. Thus, new and more effective treatments of relapse and/or means of preventing relapse are
urgently needed. It is widely believed that much of the success of allogeneic HSCT for patients with leukemia and lymphoma
is due to the graft-versus-leukemia (GVL) effect . This belief is based on the observations that GVHD correlates with superior
disease control  and that clinical responses result from maneuvers such as infusions of donor lymphocytes and withdrawing
immunosuppression . The target antigens recognized by the donor immune system are not well-characterized and certainly
are not identified in routine clinical practice .