肿瘤细胞治疗研究
英文原题：A universal chimeric antigen receptor (CAR)-fragment antibody binder (FAB) split system for cancer immunotherapy.
A universal chimeric antigen receptor (CAR)-fragment antibody binder (FAB) split system for cancer immunotherapy.
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显示出非凡的疗效，但仍面临抗原丢失、毒性以及生产制造复杂等挑战。
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显示出非凡的疗效，但面临抗原丢失、毒性和复杂制造等挑战。通用型和模块化CAR构建体相比传统CAR构建体具有更好的灵活性、安全性和成本效益。我们提出了一种基于工程化蛋白G变体（GA1）和Fab支架的CAR-片段抗体结合物（Fab）平台。GA1CAR在人CD8+ T细胞上的表达可导致抗原识别和T细胞效应功能，这些功能可根据CAR对Fab的亲和力以及Fab对靶标的亲和力进行调节。GA1CAR T细胞能够识别乳腺癌和卵巢癌细胞系上的多种Fab-抗原对。过继转移的GA1CAR T细胞在乳腺癌异种移植模型中可控制肿瘤，并且其靶向可通过使用不同的Fab快速重定向。这种多功能的“即插即用”CAR T平台在个性化治疗、防止抗原丢失变异逃逸、降低毒性和提高可及性方面具有应用潜力。
Chimeric antigen receptor (CAR) T cell therapy has shown extraordinary results in treating hematological cancer but faces challenges like antigen loss, toxicity, and complex manufacturing. Universal and modular CAR constructs offer improved flexibility, safety, and cost-effectiveness over conventional CAR constructs. We present a CAR-fragment antibody binder (Fab) platform on the basis of an engineered protein G variant (GA1) and Fab scaffolds. Expression of GA1CAR on human CD8 + T cells leads to antigen recognition and T cell effector function that can be modulated according to the affinity of the CAR for the Fab and of the Fab for the target. GA1CAR T cells can recognize multiple Fab-antigen pairs on breast and ovarian cancer cell lines. Adoptively transferred GA1CAR T cells control tumors in breast cancer xenograft models, and their targeting can be quickly redirected using different Fabs. This versatile "plug-and-play" CAR T platform has potential for application in personalized therapy, preventing antigen loss variant escape, decreasing toxicity, and increasing access.
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