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立体定向过继转移细胞毒性免疫细胞至原位多形性胶质母细胞瘤人源异种移植小鼠模型中。

Stereotactic Adoptive Transfer of Cytotoxic Immune Cells in Murine Models of Orthotopic Human Glioblastoma Multiforme Xenografts.

作者信息

Jarry Ulrich, Joalland Noémie, Chauvin Cynthia, Clemenceau Béatrice, Pecqueur Claire, Scotet Emmanuel

机构信息

INSERM, CNRS, Université d'Angers, Université de Nantes, CRCINA; Immunotherapy, Graft, Oncology, LabEx IGO.

INSERM, CNRS, Université d'Angers, Université de Nantes, CRCINA; Immunotherapy, Graft, Oncology, LabEx IGO; Hopital de Nantes, Hotel Dieu.

出版信息

J Vis Exp. 2018 Sep 1(139):57870. doi: 10.3791/57870.

Abstract

Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain cancer in adults, is generally associated with a poor prognosis, and scarce efficient therapies have been proposed over the last decade. Among the promising candidates for designing novel therapeutic strategies, cellular immunotherapies have been targeted to eliminate highly invasive and chemo-radioresistant tumor cells, likely involved in a rapid and fatal relapse of this cancer. Thus, administration(s) of allogeneic GBM-reactive immune cell effectors, such as human Vϒ9Vδ2 T lymphocytes, in the vicinity of the tumor would represents a unique opportunity to deliver efficient and highly concentrated therapeutic agents directly into the site of brain malignancies. Here, we present a protocol for the preparation and the stereotaxic administration of allogeneic human lymphocytes in immunodeficient mice carrying orthotopic human primary brain tumors. This study provides a preclinical proof-of-concept for both the feasibility and the antitumor efficacy of these cellular immunotherapies that rely on stereotactic injections of allogeneic human lymphocytes within intrabrain tumor beds.

摘要

多形性胶质母细胞瘤(GBM)是成人中最常见且侵袭性最强的原发性脑癌,通常预后较差,在过去十年中几乎没有提出有效的治疗方法。在设计新型治疗策略的有前景的候选方法中,细胞免疫疗法旨在消除高度侵袭性和放化疗抗性的肿瘤细胞,这些细胞可能与该癌症的快速致命复发有关。因此,在肿瘤附近给予同种异体GBM反应性免疫细胞效应器,如人Vγ9Vδ2 T淋巴细胞,将为直接将高效且高度浓缩的治疗剂递送至脑恶性肿瘤部位提供独特的机会。在此,我们展示了一种在携带原位人原发性脑肿瘤的免疫缺陷小鼠中制备和立体定向给予同种异体人淋巴细胞的方案。这项研究为这些依赖于在脑内肿瘤床立体定向注射同种异体人淋巴细胞的细胞免疫疗法的可行性和抗肿瘤疗效提供了临床前概念验证。

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