Development of a New Stem Cell Transplantation Procedure for Prevention of Graft-Versus-Host Disease in MM Patients

Sofi Yado, Chemical Engineering , Ariel University, Ariel, Israel
Galia Luboshits, Chemical Engineering , Ariel University, Ariel, Israel
Michael A. Firer, Chemical Engineering , Ariel University, Ariel, Israel

Despite recent advances in immuno- and chemotherapy of Multiple Myeloma (MM), a plasma cell malignancy, the disease recurs in virtually all patients. Therefore, other therapeutic approaches are needed. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is an effective treatment that can provide partial or complete remission for patients with MM where mature T cells play a central role in mediating graft-versus-myeloma (GvM) response. However, alloHSCT anti MM effect is limited, because of the development of graft-versus-host disease (GvHD), mediated by the donor T cell response against the patient’s tissues. GvHD can produce both an acute and chronic disease which can be life threatening. Based on recent TCR Vβ CDR3-size spectratype analysis to identify T cells involved in antihost and antitumor reactivity, we tested the potential of integrating autologous hematopoietic stem cell transplantation (autoHSCT) with allogeneic donor Vβ 2, 3 and 8.3-positive T cells as treatment for MM. Initially, we observed the GvM effects of alloHSCT from B10.D2 mice in 94% of MOPC315.BM-bearing Balb/c mice, whereas all the autologous transplanted mice showed myeloma progression. The alloHSCT treated mice showed lower serum paraprotein levels and lower myeloma infiltration in bone marrow and spleen, but displayed chronic GvHD symptoms. Next, we integrated autoHSCT with infusion of donor Vβ 2, 3 and 8.3-positive allogeneic T cells. The results demonstrate the involvement of Vβ 2, 3 and 8.3 positive T cell subsets in the generation of a GvM response in MM bearing mice and enhancement of survival of treated mice. Importantly, this GvM response was not accompanied by the development of GvHD. Nonetheless, the GvM response was not sufficient to completely inhibit relapse. Current experiments aim to optimize the treatment protocol so as to further enhance the GvM response.