MULTI-CHAIN CHIMERIC ANTIGEN RECEPTOR AND USES THEREOF

The present invention is directed to a new generation of chimeric antigen receptors (CAR)， which are referred to as multi-chain CARs. These CARs， which aim to re-immune cell specificity and reactivity towards a selected target utilizing ligand-binding domain properties， these CARs are signaling domains in other transmembrane polypeptides and isolated extracellular ligand binding ( binding). Signaling domains are designed to be assembled in the juxtamembrane position， which forms a flexible structure closer to the natural receptor that confers optimal signal transduction. The present invention includes isolated cells expressing them on their surface and vectors encoding the multi-chain CAR， polynucleotides， in particular their use in immunotherapy. The present invention opens the way to efficient， adoptive immunotherapy strategies for treating cancer and viral infections. The present invention relates to the generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs. Such CARs， which aim to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties， comprise separate extracellular ligand binding and signaling domains in different transmembrane polypeptides. The signaling domains are designed to assemble in juxtamembrane position， which forms flexible architecture closer to natural receptors， that confers optimal signal transduction. The invention encompasses the polynucleotides， vectors encoding said multi- chain CAR and the isolated cells expressing them at their surface， in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer and viral infections. The present invention relates to the generation of chimeric antigen receptors (CAR) referred to as multi-chain CARs. Such CARs， which aim to redirect immune cell specificity and reactivity toward a selected target exploiting the ligand-binding domain properties， comprise separate extracellular ligand binding and signaling domains in different transmembrane polypeptides. The signaling domains are designed to assemble in juxtamembrane position， which forms flexible architecture closer to natural receptors， that confers optimal signal transduction. The invention encompasses the polynucleotides， vectors encoding said multi- chain CAR and the isolated cells expressing them at their surface， in particularly for their use in immunotherapy. The invention opens the way to efficient adoptive immunotherapy strategies for treating cancer and viral infections.

本发明涉及新一代嵌合抗原受体（chimeric antigen receptor, CAR），此类受体被称为多链CAR。此类CAR旨在利用配体结合结构域的特性，将免疫细胞的特异性与反应性重定向至选定靶标；其在不同的跨膜多肽中分别包含独立的细胞外配体结合结构域与信号结构域。信号结构域被设计为在膜近侧位置组装，由此形成更接近天然受体的柔性结构，从而实现最优的信号转导。本发明涵盖了在其表面表达此类受体的分离细胞、编码多链CAR的载体以及多核苷酸，尤其涉及它们在免疫治疗中的应用。本发明为治疗癌症与病毒感染的高效过继免疫治疗策略开辟了全新路径。
本发明涉及被称为多链CAR的嵌合抗原受体的构建。此类CAR旨在利用配体结合结构域的特性，将免疫细胞的特异性与反应性重定向至选定靶标，其在不同的跨膜多肽中分别包含独立的细胞外配体结合结构域与信号结构域。信号结构域被设计为在膜近侧位置组装，由此形成更接近天然受体的柔性架构，从而赋予最优的信号转导能力。本发明涵盖了多核苷酸、编码所述多链CAR的载体，以及在其表面表达此类受体的分离细胞，尤其适用于免疫治疗领域。本发明为治疗癌症与病毒感染的高效过继免疫治疗策略开辟了路径。
本发明同样涉及被称为多链CAR的嵌合抗原受体的构建。此类CAR旨在通过利用配体结合结构域的特性，重定向免疫细胞对选定靶标的特异性与反应性，其在不同的跨膜多肽中包含相互独立的细胞外配体结合结构域与信号结构域。信号结构域被设计为在膜近侧位置组装，由此形成更贴近天然受体的柔性结构，从而实现最优的信号转导效果。本发明涵盖了多核苷酸、编码所述多链CAR的载体，以及在其表面表达此类受体的分离细胞，尤其可用于免疫治疗场景。本发明为治疗癌症与病毒感染的高效过继免疫治疗策略提供了全新的发展方向。