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Titolo:
Engineering hematopoietic grafts: Purified allogeneic hematopoietic stem cells plus expanded CD8(+) NK-T cells in the treatment of lymphoma
Autore:
Verneris, MR; Ito, M; Baker, E; Arshi, A; Negrin, RS; Shizuru, JA;
Indirizzi:
Stanford Univ, Div Bone Marrow Transplantat, Sch Med, Dept Med, Stanford, CA 94305 USA Stanford Univ Stanford CA USA 94305 Med, Dept Med, Stanford, CA 94305 USA
Titolo Testata:
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
fascicolo: 10, volume: 7, anno: 2001,
pagine: 532 - 542
SICI:
1083-8791(2001)7:10<532:EHGPAH>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; NATURAL-KILLER-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC MYELOGENOUS LEUKEMIA; MULTIPLE-MYELOMA; MOLECULE QA-1(B); LYMPHOCYTES; PERFORIN; RECOGNITION;
Keywords:
hematopoietic cell transplantation; expanded CD8(+) NK-T cells; lymphoma; graft-versus-tumor effect; GVHD; hematopoietic stem cell; mice;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Shizuru, JA Stanford Univ, Div Bone Marrow Transplantat, Sch Med, Dept Med, Room H1353, Stanford, CA 94305 USA Stanford Univ Room H1353 Stanford CA USA 94305 d, CA 94305 USA
Citazione:
M.R. Verneris et al., "Engineering hematopoietic grafts: Purified allogeneic hematopoietic stem cells plus expanded CD8(+) NK-T cells in the treatment of lymphoma", BIOL BLOOD, 7(10), 2001, pp. 532-542

Abstract

A major benefit of allogeneic hematopoietic cell transplantation (HCT) in the treatment of malignancies is the graft-versus-tumor (GVT) effect conferred by lymphocytes contained within the graft. However, lymphocytes can also induce the potentially lethal complication of graft-versus-host disease (GVHD). We have previously reported a method of generating large numbers of ex vivo activated and expanded T cells with antitumor activity after culture with interferon-gamma, cross-linking antibodies to CD3, and interleukin-2. Murine splenocytes expanded under these conditions are a heterogeneous population of which approximately 20% to 60% of cells express natural killer (NK)-cell markers (NK1.1 and DX5) and display major histocompatibility complex (MHC)-unrestricted antitumor activity. Here we demonstrate the in vivo antitumor activity of this population of expanded CD8(+) NK-T cells when transplanted across MHC barriers into tumor-beating hosts. In cotransfer studies with purified allogeneic hematopoietic stem cells, expanded CD8(+) NK-Tcells confer GVT activity with minimal to no GVHD. In vitro studies show that, although expanded NK-T cells lyse normal allogeneic bone marrow cells,they preferentially mediate cytolysis against tumor targets. These cells persist in the peripheral circulation of host animals for at least 3 weeks posttransfer. GVT activity is dependent on perforin, but not on Fas-ligand. We conclude that expanded CD8(+) NK-T cells may serve as a valuable adjuvant population for allogeneic HCT because they mediate GVT effects with minimal GVHD.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/03/20 alle ore 23:34:12