抗 CD22/CD19 CAR-T 细胞疗法 CART2219.1 在成人和儿童复发/难治性 B-ALL 中的 I/II 期试验
A Phase I/II Trial of Anti-CD22/CD19 CAR-T Cell Therapy, CART2219.1, in Adult and Pediatric Relapsed/Refractory B-ALL.
在一项多中心I/II期试验中,所有患者(n=11;7名儿童,4名成人)在第28天均达到完全缓解(91%为微小残留病阴性)。
英文原题:Evaluation of the safety and efficiency of cytotoxic T cell therapy sensitized by tumor antigens original from T-ALL-iPSC in vivo.
基于T-ALL-iPSC的治疗是安全的,可作为白血病免疫治疗的一种潜在策略。
由于 RNA 测序显示诱导多能干细胞 (iPSCs) 与肿瘤细胞具有共同的抗原谱,近年来聚焦于 iPSCs 的癌症疫苗取得了令人瞩目的进展。此前,我们已经证明,来源于原发性 T 细胞急性淋巴细胞白血病 (T-ALL) 患者白血病细胞的 iPSCs 具有与 T-ALL 细胞系相似的基因表达谱。
用负载T-ALL来源iPSCs(T-ALL-iPSCs)完整抗原的树突状细胞和T(DC-T)细胞治疗T-ALL小鼠。我们通过流式细胞术、细胞因子释放试验、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果。
我们的结果表明,来自T-ALL-iPSCs的完整肿瘤抗原能够抑制免疫缺陷小鼠中接种肿瘤的生长,且不会引起急性和长期毒性。
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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