Robert Negrin

Publication Details

  • A new approach for eradication of residual lymphoma cells by host nonreactive anti-third-party central memory CD8 T cells BLOOD Lask, A., Ophir, E., Or-Geva, N., Cohen-Fredarow, A., Afik, R., Eidelstein, Y., Reich-Zeliger, S., Nathansohn, B., Edinger, M., Negrin, R. S., Hagin, D., Reisner, Y. 2013; 121 (15): 3033-3040

    Abstract:

    Generation of T cells endowed with graft-versus-leukemia (GVL) and depleted of graft-versus-host (GVH) activity represents a highly desirable goal in bone marrow transplantation (BMT). Here, we demonstrate that donor anti-third-party CD8 T cells with central memory phenotype (Tcm) exhibit marked GVL reactivity through a unique T-cell receptor-independent mechanism. Thus, in a residual disease mouse model, Tcm therapy following autologous BMT led to significant survival prolongation, with 30% to 40% of the treated mice displaying long-term tumor-free survival. A more impressive finding was that infusion of donor Tcm in an allogeneic model rapidly eliminated residual lymphoma cells and led to long-term survival of 100% in the absence of GVH disease. Collectively, the strong GVL reactivity of anti-third-party Tcm, coupled with their demonstrated enhancement of bone marrow allografting, suggests that the use of Tcm therapy in conjunction with allogeneic T-cell-depleted BMT could be of particular benefit in patients with B-cell malignancies who cannot tolerate intensive myeloablative conditioning.

    View details for DOI 10.1182/blood-2012-06-432443

    View details for Web of Science ID 000321825700028

    View details for PubMedID 23446736

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