肿瘤细胞治疗研究
英文原题：CD22 TCR-engineered T cells exert antileukemia cytotoxicity without causing inflammatory responses.
嵌合抗原受体（CAR）T细胞能有效治疗B细胞恶性肿瘤。
嵌合抗原受体（CAR）T细胞可有效治疗B细胞恶性肿瘤。然而，CAR-T细胞会引起细胞因子释放综合征（CRS）等炎症毒性，这与针对多种抗原的T细胞受体（TCR）工程化T细胞形成对比，后者在历史上很少与CRS相关。为了在TCR和CAR靶向同等临床相关抗原来源的模型系统中研究受体类型差异是否以及如何影响引发炎症反应的倾向，我们发现了一种CD22特异性TCR，并将其与CD22 CAR进行比较。CD22 TCR-T和CD22 CAR-T细胞均能在异种移植模型中清除白血病，但只有CD22 CAR-T细胞诱导了剂量依赖性的全身炎症。与TCR-T细胞相比，CAR-T细胞在抗原结合后不成比例地上调炎症通路，而参与直接细胞毒性的通路并未相应增强。比较TCR-T和CAR-T细胞抗白血病反应的这些差异，凸显了通过使用TCR提高治疗安全性的潜在机会。
Chimeric antigen receptor (CAR) T cells effectively treat B cell malignancies. However, CAR-T cells cause inflammatory toxicities such as cytokine release syndrome (CRS), which is in contrast to T cell receptor (TCR)-engineered T cells against various antigens that historically have rarely been associated with CRS. To study whether and how differences in receptor types affect the propensity for eliciting inflammatory responses in a model system wherein TCR and CAR target equalized sources of clinically relevant antigen, we discovered a CD22-specific TCR and compared it to CD22 CAR. Both CD22 TCR-T and CD22 CAR-T cells eradicated leukemia in xenografts, but only CD22 CAR-T cells induced dose-dependent systemic inflammation. Compared to TCR-T cells, CAR-T cells disproportionately upregulated inflammatory pathways without concordant augmentation in pathways involved in direct cytotoxicity upon antigen engagement. These differences in antileukemia responses comparing TCR-T and CAR-T cells highlight the potential opportunity to improve therapeutic safety by using TCRs.
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