title: A new approach for eradication of residual lymphoma cells by host nonreactive anti-third-party central memory CD8 T cells.
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.
authors: Immunology Department, Weizmann Institute of Science, Rehovot, Israel.
authors: Assaf
authors: A
authors: Lask
authors: Eran
authors: E
authors: Ophir
authors: Noga
authors: N
authors: Or-Geva
authors: Adva
authors: A
authors: Cohen-Fredarow
authors: Ran
authors: R
authors: Afik
authors: Yaki
authors: Y
authors: Eidelstein
authors: Shlomit
authors: S
authors: Reich-Zeliger
authors: Bar
authors: B
authors: Nathansohn
authors: Matthias
authors: M
authors: Edinger
authors: Robert S
authors: RS
authors: Negrin
authors: David
authors: D
authors: Hagin
authors: Yair
authors: Y
authors: Reisner
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000379:methods; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D020544:Graft vs Leukemia Effect / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism; D008223:Lymphoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D018365:Neoplasm, Residual / Q000276:immunology*; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1