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

Cancer Innovation Pub Date : 2023-10-19 DOI:10.1002/cai2.95
Weiran Li, Meiling Zhou, Lu Wang, Liying Huang, Xuemei Chen, Xizhuo Sun, Tao Liu
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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

T-ALL-iPSC-based treatment is safe and can be used as a potential strategy for leukemia immunotherapy.

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评估由 T-ALL-iPSC 原始肿瘤抗原致敏的细胞毒性 T 细胞疗法在体内的安全性和效率
背景 由于 RNA 测序显示诱导多能干细胞(iPSC)与肿瘤细胞具有共同的抗原谱,因此近年来以 iPSC 为研究对象的癌症疫苗取得了可喜的进展。此前,我们曾发现,从原发性 T 细胞急性淋巴细胞白血病(T-ALL)患者的白血病细胞中提取的 iPSCs 具有与 T-ALL 细胞系相似的基因表达谱。 方法 用树突状细胞和 T(DC-T)细胞治疗 T-ALL 小鼠,树突状细胞和 T(DC-T)细胞含有来自 T-ALL 的 iPSCs(T-ALL-iPSCs)的完整抗原。我们通过流式细胞术、细胞因子释放检测、急性毒性实验、长期毒性实验等方法评估了自体肿瘤衍生 iPSC 抗原的安全性和抗肿瘤效率。 结果 我们的研究结果表明,T-ALL-iPSCs 的完整肿瘤抗原可抑制免疫缺陷小鼠接种肿瘤的生长,且不会引起急性和长期毒性。 结论 基于 TALL-iPSC 的治疗是安全的,可作为一种潜在的白血病免疫治疗策略。
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