现成的第三方造血干细胞工程化不变自然杀伤T细胞，用于在治疗血癌时减轻移植物抗宿主病（GvHD）同时保留移植物抗白血病效应（GvL） 。
Off-the-shelf third-party HSC-engineered iNKT cells for ameliorating GvHD while preserving GvL effect in the treatment of blood cancers.
作者信息
Li Yan-Ruide, Zeng Samuel, Dunn Zachary Spencer, Zhou Yang, Li Zhe, Yu Jiaji, Wang Yu-Chen, Ku Josh, Cook Noah, Kramer Adam, Yang Lili
机构信息
Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
出版信息
iScience. 2022 Aug 6;25(9):104859. doi: 10.1016/j.isci.2022.104859. eCollection 2022 Sep 16.
Allo-HSCT is a curative therapy for hematologic malignancies owing to GvL effect mediated by alloreactive T cells; however, the same T cells also mediate GvHD, a severe side effect limiting the widespread application of allo-HSCT in clinics. Invariant natural killer T (iNKT) cells can ameliorate GvHD while preserving GvL effect, but the clinical application of these cells is restricted by their scarcity. Here, we report the successful generation of third-party HSC-engineered human iNKT (HSC-iNKT) cells using a method combining HSC gene engineering and HSC differentiation. The HSC-iNKT cells closely resembled the CD4CD8 subsets of endogenous human iNKT cells in phenotype and functionality. These cells displayed potent anti-GvHD functions by eliminating antigen-presenting myeloid cells and in xenograft models without negatively impacting tumor eradication by allogeneic T cells in preclinical models of lymphoma and leukemia, supporting HSC-iNKT cells as a promising off-the-shelf cell therapy candidate for GvHD prophylaxis.
异基因造血干细胞移植（Allo-HSCT）是一种治疗血液系统恶性肿瘤的有效疗法，这得益于同种反应性T细胞介导的移植物抗白血病（GvL）效应；然而，同样是这些T细胞也介导移植物抗宿主病（GvHD），这是一种严重的副作用，限制了Allo-HSCT在临床上的广泛应用。不变自然杀伤T（iNKT）细胞可以改善GvHD，同时保留GvL效应，但这些细胞的临床应用受到其稀缺性的限制。在这里，我们报告了通过将造血干细胞（HSC）基因工程与HSC分化相结合的方法成功生成第三方HSC工程化人iNKT（HSC-iNKT）细胞。HSC-iNKT细胞在表型和功能上与内源性人iNKT细胞的CD4CD8亚群非常相似。在淋巴瘤和白血病的临床前模型中，这些细胞通过消除抗原呈递髓样细胞显示出强大的抗GvHD功能，并且在异种移植模型中不会对同种异体T细胞根除肿瘤产生负面影响，这支持HSC-iNKT细胞作为一种有前途的现成细胞疗法候选物用于预防GvHD。
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