肿瘤细胞治疗研究
英文原题：IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors.
IKZF3 deficiency potentiates chimeric antigen receptor T cells targeting solid tumors.
我们的结果提示了一种增强CAR T在实体瘤中疗效的通用策略。
嵌合抗原受体（CAR）T细胞疗法在治疗血液系统恶性肿瘤方面已取得成功，但实体瘤仍然难治。在此，我们证明，在靶向乳腺癌细胞的HER2特异性CAR T细胞中敲除转录因子IKZF3不影响CAR表达或CAR T细胞分化，但显著增强了体外和异种移植模型中对癌细胞的杀伤，这与T细胞活化和增殖增加相关。此外，IKZF3 KO对靶向胶质母细胞瘤细胞的CD133特异性CAR T细胞具有类似效果。AlphaLISA和RNA-seq分析表明，IKZF3 KO增加了参与细胞因子信号传导、趋化和细胞毒性的基因的表达。我们的结果提出了一种增强CAR T对实体瘤疗效的通用策略。
Chimeric antigen receptor (CAR) T cell therapy has been successful in treating hematological malignancy, but solid tumors remain refractory. Here, we demonstrated that knocking out transcription factor IKZF3 in HER2-specific CAR T cells targeting breast cancer cells did not affect CAR expression or CAR T cell differentiation, but markedly enhanced killing of the cancer cells in vitro and in a xenograft model, which was associated with increased T cell activation and proliferation. Furthermore, IKZF3 KO had similar effects on the CD133-specific CAR T cells targeting glioblastoma cells. AlphaLISA and RNA-seq analyses indicate that IKZF3 KO increased the expression of genes involved in cytokine signaling, chemotaxis and cytotoxicity. Our results suggest a general strategy for enhancing CAR T efficacy on solid tumors.
MEMBER ACCOUNT
登录成功会直接打开下一页。
