Sanz Marta, Mann Brendan T, McMahon Elyse K, Bosque Alberto, Simmens Samuel, Soriano-Sarabia Natalia
Departments of Microbiology Immunology and Tropical Medicine, George Washington University, Washington, DC 20037, USA.
Biostatistics, George Washington University, Washington, DC 20037, USA.
Mol Ther Oncol. 2025 May 14;33(2):200996. doi: 10.1016/j.omton.2025.200996. eCollection 2025 Jun 18.
The increasing success of allogenic Vδ2 T cell immunotherapy for the treatment of cancer has been demonstrated in recent studies. Vδ2 T cells recognize phosphoantigens, intermediates of the mevalonate pathway, through butyrophilin molecules, and they are not major histocompatibility complex (MHC) restricted. Allogeneic transfer of expanded Vδ2 T cells has shown more promising results than autologous strategies, although the clinical benefit remains limited. One of the issues leading to less-than-optimal responses relates to the polyclonal expansion of Vδ2 T cell subsets with variable cytotoxic capacity. Previous work developed protocols to expand Vδ2 T cells, although to our knowledge, ours is the first comprehensive study that has produced a simple, antigen-presenting feeder-free culture that produced an average expansion of 3,000-fold and more than 95% pure Vδ2 T cells avoiding additional isolation steps. Here, we show the expansion of cytotoxic Vδ2 T cells expressing CD16 and NKG2A enriched in granzyme B that displayed enhanced antitumor activity of up to 40% against leukemia and ovarian, breast, and lung cancer cells. Our work warrants clinical testing to evaluate the therapeutic potential of these highly cytotoxic cells, paving the way for improved efficacy of personalized cell-based immunotherapies.
近期研究已证实同种异体Vδ2 T细胞免疫疗法在癌症治疗中越来越成功。Vδ2 T细胞通过嗜乳脂蛋白分子识别磷酸抗原（甲羟戊酸途径的中间体），且不受主要组织相容性复合体（MHC）限制。尽管临床益处仍然有限，但扩增后的Vδ2 T细胞的同种异体转移已显示出比自体策略更有前景的结果。导致反应未达最佳效果的问题之一与具有可变细胞毒性能力的Vδ2 T细胞亚群的多克隆扩增有关。先前的工作开发了扩增Vδ2 T细胞的方案，不过据我们所知，我们的研究是第一项全面的研究，建立了一种简单的、无抗原呈递饲养细胞的培养方法，该方法实现了平均3000倍的扩增，且Vδ2 T细胞纯度超过95%，无需额外的分离步骤。在此，我们展示了表达CD16和富含颗粒酶B的NKG2A的细胞毒性Vδ2 T细胞的扩增，这些细胞对白血病以及卵巢癌、乳腺癌和肺癌细胞显示出高达40%的增强抗肿瘤活性。我们的工作值得进行临床试验，以评估这些高细胞毒性细胞的治疗潜力，为提高个性化细胞免疫疗法的疗效铺平道路。
