CAR-T创新浪潮下，多次跨膜蛋白靶点迎来黄金期

自2017年全球首-款血液肿瘤CAR-T疗法获批以来，CAR-T领域持续迎来重要突破，不断革新肿瘤免疫治疗格局。从血液肿瘤率先“破冰”，到监管政策持续优化，再到实体瘤治疗取得历史性突破，越来越多创新靶点进入临床开发，CAR-T疗法正迈入全新的发展阶段。

2025年6月，美国FDA宣布取消已上市的CD19和BCMA靶点CAR-T疗法的风险评估与缓解策略（REMS）要求，以降低医疗机构实施CAR-T治疗的门槛，提高患者可及性，标志着CAR-T疗法已进入成熟发展阶段，为临床推广创造了有利条件。

与此同时，CAR-T的治疗边界不断向自身免疫疾病拓展。除血液肿瘤外，针对系统性红斑狼疮（SLE）、系统性硬化症等自身免疫疾病的CAR-T临床研究屡获积极进展，已成为全球研发的重要热点。

在实体瘤领域，CAR-T同样迎来里程碑式突破。2026年6月，科济药业靶向Claudin 18.2的CAR-T产品satri-cel（CT041）获中国国家药品监督管理局批准上市，用于治疗Claudin 18.2阳性晚期胃癌/胃食管结合部腺癌。这是全球首-个获批用于实体瘤治疗的CAR-T产品，标志着CAR-T正式突破实体瘤治疗瓶颈，也进一步验证了Claudin 18.2作为CAR-T靶点的临床价值。

近年来，CAR-T治疗靶点布局呈现出“成熟靶点领跑、新兴靶点突破”的态势。根据摩熵咨询发布的《CAR-T药物研发与市场全景研究报告》，截至2025年，全球CAR-T在研及上市管线达1519条，其中CD20（90条），Claudin 18.2等多次跨膜蛋白相关CAR-T管线已超过200条，占比超13%。值得关注的是，2024年新增CAR-T临床试验中实体瘤占比达42%，且实体瘤核心靶点（Claudin 18.2、Claudin 6、GPRC5D、STEAP1）均为多次跨膜蛋白。可见，多次跨膜蛋白正在成为CAR-T新兴靶点的核心力量。

数据来源：摩熵咨询《CAR-T药物研发与市场全景研究报告》

全球/中国CAR-T在研管线TOP-10靶点分布

相较于传统可溶性蛋白靶点，多次跨膜蛋白保留了完整的空间结构和膜表位，更接近天然构象，有利于CAR的识别与结合，能更真实地反映抗原结合能力，具有显著的成药潜力和临床价值。因此，越来越多的CAR-T产品开发开始围绕多次跨膜蛋白靶点展开。

多次跨膜蛋白结构复杂、表达难度大、对脂质环境依赖性强，如何获得保持天然构象和生物活性的全长多次跨膜蛋白，成为CAR-T研发的关键难题。

针对 CAR-T新兴热门靶点研发对全长多次跨膜蛋白的迫切需求，ACROBiosystems百普赛斯基于“膜杰作” Nanodisc、Nanodisc-pro、VLP、Detergent平台已开发Claudin 18.2、Claudin 6、GPRC5D、STEAP1、CD20等CAR-T热门靶点的全长多次跨膜蛋白产品，最-大程度保持多次跨膜蛋白的天然空间构象和生物学活性。

CAR阳性率检测是CAR-T细胞构建后的关键质量控制步骤，也是评价CAR表达水平和后续功能研究的基础。

在此ACROBiosystems百普赛斯重点推荐“膜杰作”Nanodisc、Nanodisc-pro、VLP平台的全长多次跨膜蛋白用于CAR阳性率检测，该类产品已通过相关验证，能为CAR-T疗法开发过程中的 CAR 阳性率检测提供真实、可靠的数据支持，精准赋能CAR-T细胞治疗的高效研发。

5e5 of Anti-CD20 CAR-293 cells were stained with 100 μL of 1:20 dilution (5 μL stock solution in 100 μL FACS buffer) of PE-Labeled Human CD20 Full Length Protein, His Tag (Nanodisc) (Cat. No. CD0-HP2E4) and negative control protein respectively. PE signal was used to evaluate the binding activity (QC tested).

2e5 of Anti-CD20 CAR-293 cells were stained with 100 μL of 10 μg/mL of Fluorescent Human CD20 Full Length Protein (VLP) (Cat. No. CDP-HF2P8) and negative control protein respectively. GFP signal was used to evaluate the binding activity (QC tested).

5e5 of Anti-Claudin 18.2 CAR-293 cells were stained with 100 μL of 1:25 dilution (4 μL stock solution in 100 μL FACS buffer) of PE-Labeled Human/Cynomolgus Claudin 18.2 Protein, His, Flag Tag (Nanodisc) (Cat. No. CL2-HP2D3) and negative control protein respectively. PE signal was used to evaluate the binding activity (QC tested).

2e5 of Anti-Claudin 18.2 CAR-293 cells were stained with 100 μL of 3 μg/mL of Fluorescent Human Claudin -18.2 Full Length Protein(VLP) (Cat. No. CL2-HF218) and negative control protein respectively, FITC signal was used to evaluate the binding activity (QC tested).

FACS Analysis of Anti-Claudin 6 CAR expression

2e5 of Anti-Claudin 6 CAR-293 cells were stained with 100 μL of 1 μg/mL of Fluorescent Human Claudin -6 Protein, Flag, His, GFP Tag (Nanodisc) (Cat. No. CL6-HF2M9) and negative control protein respectively (Fig. A and B), FITC signal was used to evaluate the binding activity (QC tested).

Flow cytometric analysis of overexpressing Anti-Claudin 6(BBz) CAR-293 cells staining with Fluorescent Human Claudin -6 Full Length Protein, Flag, His Tag, GFP Tag (Nanodisc-pro) (Cat. No. CL6-H52M3) (2e5 of Anti-Claudin -6(BBz) CAR-293 cells were stained with 100 μL of 5 μg/mL of Fluorescent Human Claudin -6 Full Length Protein, Flag, His Tag, GFP Tag, compared with negative control protein analyzed with FACS (QC tested).

2e5 of Anti-Claudin 6 CAR-293 cells were stained with 100 μL of 3 μg/mL of Fluorescent Human Claudin -6 Full Length Protein (VLP) (Cat. No. CL6-HF2G8) and negative control protein respectively. GFP signal was used to evaluate the binding activity (QC tested).

FACS Analysis of Anti-GPRC5D CAR expression

2e5 of Anti-GPRC5D CAR-293 cells were stained with 100 μL of 10 μg/mL of Fluorescent Human GPRC5D Full Length Protein (VLP) (Cat. No. GPD-HF2P7) and isotype control protein respectively. GFP signal was used to evaluate the binding activity (Routinely tested).

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