肿瘤细胞治疗研究
英文原题：Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies.
Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies.
CAR-T 细胞极大地改善了血液系统恶性肿瘤的治疗。
CAR-T 细胞已显著改善血液系统恶性肿瘤的治疗。基于T细胞抗原受体（TCR）的细胞疗法尚未达到可比的结果。重要的是，嵌合抗原受体不仅靶向选定的抗原，还通过其在抗原识别时参与的共刺激通路重编程T细胞功能。我们在此展示一种融合受体，由CD80胞外域和4-1BB胞质域组成，称为80BB，既作为配体又作为受体来参与CD28和4-1BB通路，从而增强人类白细胞抗原非依赖性TCR（HIT）受体或TCR工程化T细胞以及TIL（肿瘤浸润淋巴细胞）的抗肿瘤效力。此外，80BB作为一种开关受体，在被抑制性CTLA4分子连接时提供激动性4-1BB共刺激。通过将多种共刺激特征结合在单一抗原不可知合成受体中，80BB是一种有前景的工具，可在广泛的靶向免疫疗法中维持CD3依赖性T细胞反应。
Chimeric antigen receptor T cells have dramatically improved the treatment of hematologic malignancies. T cell antigen receptor (TCR)-based cell therapies are yet to achieve comparable outcomes. Importantly, chimeric antigen receptors not only target selected antigens but also reprogram T cell functions through the co-stimulatory pathways that they engage upon antigen recognition. We show here that a fusion receptor comprising the CD80 ectodomain and the 4-1BB cytoplasmic domain, termed 80BB, acts as both a ligand and a receptor to engage the CD28 and 4-1BB pathways, thereby increasing the antitumor potency of human leukocyte antigen-independent TCR (HIT) receptor- or TCR-engineered T cells and tumor-infiltrating lymphocytes. Furthermore, 80BB serves as a switch receptor that provides agonistic 4-1BB co-stimulation upon its ligation by the inhibitory CTLA4 molecule. By combining multiple co-stimulatory features in a single antigen-agnostic synthetic receptor, 80BB is a promising tool to sustain CD3-dependent T cell responses in a wide range of targeted immunotherapies.
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