Long-term survival without graft-versus-host-disease following infusion of allogeneic myeloma-specific Vβ T cell families

• Published in: Journal for immunotherapy of cancer 2019-11, Vol.7 (1), p.301-301, Article 301
• Main Authors: Yado, S., Luboshits, G., Hazan, O., Or, R., Firer, M. A.
• Format: Article
• Language: English
• Subjects: Adoptive allogeneic T-cell therapy; T cell–receptor Vβ families; Animals; Apathy; Basic Tumor Immunology; Bone marrow; Bone marrow transplantation; Cancer; Cytotoxicity; Experiments; Flow cytometry; Graft versus host disease; Graft-versus-myeloma; Immunotherapy; Laboratories; Lymphocytes; Mortality; Multiple myeloma; Paralysis; Research Article; Spleen; Stem cell transplantation; T cell receptors; Transplants & implants
• ISSN: 2051-1426; 2051-1426
• DOI: 10.1186/s40425-019-0776-9

BackgroundDespite chemo-induction therapy and autologous stem cell transplantation (ASCT), the vast majority of patients with Multiple Myeloma (MM) relapse within 7 years and the disease remains incurable. Adoptive Allogeneic T-cell therapy (ATCT) might be curative for MM, however current ATCT protocols often lead to graft versus host disease (GvHD). Transplanting only tumor reactive donor T cells that mediate a graft-versus-myeloma (GvM) but not GvHD may overcome this problem.MethodsWe used an MHC-matched/miHA-disparate B10.D2 → Balb/c bone marrow transplantation (BMT) murine model and MOPC315.BM MM cells to develop an ATCT protocol consisting of total body irradiation, autologous-BMT and infusion of selective, myeloma-reactive lymphocytes of T cell receptor (TCR) Vβ 2, 3 and 8.3 families (MM-auto BMT ATCT).ResultsPre-stimulation ex vivo of allogeneic T cells by exposure to MOPC315.BM MM cells in the presence of IL-2, anti-CD3 and anti-CD28 resulted in expansion of the myeloma-reactive T cell TCRVβ 2, 3 and 8.3 subfamilies. Their isolation and infusion into MM-bearing mice resulted in a vigorous GvM response without induction GvHD and long-term survival. Repeated infusion of naïve myeloma-reactive T cell TCRVβ 2, 3 and 8.3 subfamilies was also effective.ConclusionsThese data demonstrate that a transplantation protocol involving only selective tumor-reactive donor T cell families is an effective immunotherapy and results in long-term survival in a mouse model of human MM. The results highlight the need to develop similar ATCT strategies for MM patients that result in enhanced survival without symptoms of GvHD.