研究动态
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体内 T-ALL-iPSC 肿瘤抗原致敏的细胞毒性 T 细胞疗法的安全性和有效性评估。

Evaluation of the safety and efficiency of cytotoxic T cell therapy sensitized by tumor antigens original from T-ALL-iPSC in vivo.

发表日期:2024 Feb
作者: Weiran Li, Meiling Zhou, Lu Wang, Liying Huang, Xuemei Chen, Xizhuo Sun, Tao Liu
来源: CYTOKINE & GROWTH FACTOR REVIEWS

摘要:

由于RNA测序表明诱导多能干细胞(iPSC)与肿瘤细胞具有共同的抗原谱,因此针对iPSC的癌症疫苗近年来取得了可喜的进展。此前,我们发现源自原发性T细胞急性淋巴细胞白血病(T-ALL)患者白血病细胞的iPSC具有与T-ALL细胞系相似的基因表达谱。患有T-ALL的小鼠接受了树突状和T细胞治疗。 (DC-T) 细胞装载有来自 T-ALL 衍生 iPSC (T-ALL-iPSC) 的完整抗原。我们通过流式细胞术、细胞因子释放实验、急性毒性实验、长期毒性实验等方法评估了自体肿瘤来源iPSC抗原的安全性和抗肿瘤效率。我们的结果表明,来自T-ALL-iPSC的完整肿瘤抗原可以抑制免疫功能低下小鼠中接种肿瘤的生长,而不引起急性和长期毒性。基于 T-ALL-iPSC 的治疗是安全的,可用作白血病免疫治疗的潜在策略。© 2023 作者。约翰·威利 (John Wiley) 出版的《癌症创新》
Since RNA sequencing has shown that induced pluripotent stem cells (iPSCs) share a common antigen profile with tumor cells, cancer vaccines that focus on iPSCs have made promising progress in recent years. Previously, we showed that iPSCs derived from leukemic cells of patients with primary T cell acute lymphoblastic leukemia (T-ALL) have a gene expression profile similar to that of T-ALL cell lines.Mice with T-ALL were treated with dendritic and T (DC-T) cells loaded with intact and complete antigens from T-ALL-derived iPSCs (T-ALL-iPSCs). We evaluated the safety and antitumor efficiency of autologous tumor-derived iPSC antigens by flow cytometry, cytokine release assay, acute toxicity experiments, long-term toxicity experiments, and other methods.Our results indicate that complete tumor antigens from T-ALL-iPSCs could inhibit the growth of inoculated tumors in immunocompromised mice without causing acute and long-term toxicity.T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.© 2023 The Authors. Cancer Innovation published by John Wiley & Sons Ltd. on behalf of Tsinghua University Press.