Immunomodulation with dendritic cells and donor lymphocyte infusion converge to induce graft vs neuroblastoma reactions without GVHD after allogeneic bone marrow transplantation

被引：16

作者：

Ash, S. ^{[2
,3
]}

Stein, J. ^{[2
,4
]}

Askenasy, N. ^{[1
]}

Yaniv, I. ^{[2
,3
]}

机构：

[1] Schneider Childrens Med Ctr Israel, Frankel Lab Expt Bone Marrow Transplantat, IL-49202 Petah Tiqwa, Israel

[2] Schneider Childrens Med Ctr Israel, Dept Pediat Hematol Oncol, IL-49202 Petah Tiqwa, Israel

[3] Schneider Childrens Med Ctr Israel, Zaizov Canc Immunotherapy Lab, IL-49202 Petah Tiqwa, Israel

[4] Schneider Childrens Med Ctr Israel, Pediat Bone Marrow Transplant Unit, IL-49202 Petah Tiqwa, Israel

来源：

BRITISH JOURNAL OF CANCER | 2010年 / 103卷 / 10期

关键词：

neuroblastoma; allogeneic bone marrow transplantation; dendritic cells; donor lymphocyte infusion; graft vs tumour reaction; graft vs host disease; VERSUS-HOST-DISEASE; ANTIGEN-PRESENTING CELLS; ANTITUMOR IMMUNE-RESPONSES; MEMORY T-CELLS; SOLID TUMORS; LEUKEMIA RESPONSES; IMMUNOTHERAPY; CHILDREN; PREVENTION; EXPRESSION;

D O I：

10.1038/sj.bjc.6605924

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BACKGROUND: Mounting evidence points to the efficacy of donor lymphocyte infusion (DLI) and immunisation with tumour-pulsed dendritic cells (DC) in generating graft vs leukaemia reactions after allogeneic bone marrow transplantation (BMT). We assessed the efficacy of DLI and DC in generating potent graft vs neuroblastoma tumour (GVT) reactions following allogeneic BMT. METHODS: Mice bearing congenic (H2K(a)) Neuro-2a tumours were grafted with allogeneic (H2K(b)) T-cell-depleted bone marrow cells. Tumour-pulsed donor DC (DCNeuro2a) were inoculated (on day +7) in conjunction with donor (H2K(b)) and haploidentical (H2K(a/b)) lymphocytes. RESULTS: Murine Neuro-2a cells elicit immune reactions as efficient as B lymphoma in major histocompatibility complex antigen-disparate mice. Lymphopenia induced by conditioning facilitates GVT, and transition to adaptive immunity is enhanced by simultaneous infusion of and DCNeuro2a and lymphocytes devoid of graft vs host (GVH) activity (H2K(a/b)). In variance, the efficacy of DC-mediated immunomodulation was diminished by severe graft vs host disease (GVHD), showing mechanistic dissociation and antagonising potential to GVT. CONCLSIONS: The GVHD is not a prerequisite to induce GVT reactivity after allogeneic BMT, but is rather detrimental to induction of anti-tumour immunity by DC-mediated immunomodulation. Simultaneous inoculation of tumour-pulsed donor DC and DLI synergise in stimulation of potent GVT reactions to the extent of eradication of established NB tumours. British Journal of Cancer (2010) 103, 1597-1605. doi:10.1038/sj.bjc.6605924 www.bjcancer.com Published online 26 October 2010 (C) 2010 Cancer Research UK

引用

页码：1597 / 1605

页数：9

共 58 条

[1] Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease [J].