同种异体人Vγ9Vδ2 T细胞的立体定向给药有效控制人胶质母细胞瘤脑肿瘤的发展。

Stereotaxic administrations of allogeneic human Vγ9Vδ2 T cells efficiently control the development of human glioblastoma brain tumors.

作者信息

Jarry Ulrich, Chauvin Cynthia, Joalland Noémie, Léger Alexandra, Minault Sandrine, Robard Myriam, Bonneville Marc, Oliver Lisa, Vallette François M, Vié Henri, Pecqueur Claire, Scotet Emmanuel

机构信息

INSERM, U892, Nantes, France, Univ Nantes, Nantes, France, CNRS, UMR 6299, Nantes, France; LabEx IGO, "Immunotherapy Graft Oncology", Nantes, France.

INSERM, U892, Nantes, France, Univ Nantes, Nantes, France, CNRS, UMR 6299 , Nantes, France.

出版信息

Oncoimmunology. 2016 Mar 30;5(6):e1168554. doi: 10.1080/2162402X.2016.1168554. eCollection 2016 Jun.

Abstract

Glioblastoma multiforme (GBM) represents the most frequent and deadliest primary brain tumor. Aggressive treatment still fails to eliminate deep brain infiltrative and highly resistant tumor cells. Human Vγ9Vδ2 T cells, the major peripheral blood γδ T cell subset, react against a wide array of tumor cells and represent attractive immune effector T cells for the design of antitumor therapies. This study aims at providing a preclinical rationale for immunotherapies in GBM based on stereotaxic administration of allogeneic human Vγ9Vδ2 T cells. The feasibility and the antitumor efficacy of stereotaxic Vγ9Vδ2 T cell injections have been investigated in orthotopic GBM mice model using selected heterogeneous and invasive primary human GBM cells. Allogeneic human Vγ9Vδ2 T cells survive and patrol for several days within the brain parenchyma following adoptive transfer and can successfully eliminate infiltrative GBM primary cells. These striking observations pave the way for optimized stereotaxic antitumor immunotherapies targeting human allogeneic Vγ9Vδ2 T cells in GBM patients.

摘要

多形性胶质母细胞瘤(GBM)是最常见且最致命的原发性脑肿瘤。积极的治疗仍无法清除脑深部浸润且高度耐药的肿瘤细胞。人类Vγ9Vδ2 T细胞是外周血中主要的γδ T细胞亚群,可对多种肿瘤细胞产生反应,是设计抗肿瘤疗法极具吸引力的免疫效应T细胞。本研究旨在为基于立体定向给予异体人类Vγ9Vδ2 T细胞的GBM免疫疗法提供临床前理论依据。使用选定的异质性和侵袭性原发性人类GBM细胞,在原位GBM小鼠模型中研究了立体定向Vγ9Vδ2 T细胞注射的可行性和抗肿瘤疗效。异体人类Vγ9Vδ2 T细胞在过继转移后可在脑实质内存活并巡逻数天,并能成功清除浸润性GBM原代细胞。这些显著的观察结果为针对GBM患者中人类异体Vγ9Vδ2 T细胞的优化立体定向抗肿瘤免疫疗法铺平了道路。

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