肿瘤细胞治疗研究
英文原题：Comparing Intraperitoneal and Intravenous Personalized ErbB2CAR-T for the Treatment of Epithelial Ovarian Cancer.
这些数据展示了CAR-T细胞腹腔注射相较于静脉注射的优势，不仅提供了一种更安全的策略，还具有对抗HGSOC中ErbB2CAR效果的潜力。
高级别浆液性卵巢癌（HGSOC）是最常见的上皮性卵巢癌类型。大多数病例在确诊时已处于晚期，此时腹腔内（IP）播散已经发生。尽管过去几十年中HGSOC治疗在手术和化疗方面取得了显著进展，但HGSOC的生存率仅略有改善。嵌合抗原受体（CAR）-T细胞使T细胞能够以不依赖主要组织相容性复合体的方式直接结合肿瘤相关抗原，从而诱导肿瘤排斥。虽然CAR-T细胞疗法在血液系统恶性肿瘤中展现出巨大前景，但其在实体瘤中的应用受到限制。因此，需要创新方法来提高CAR修饰T细胞对实体瘤的特异性。本研究旨在评估腹腔内（IP）与静脉内（IV）CAR-T细胞疗法在治疗HGSOC中的疗效和安全性。我们构建了一种靶向ErbB2/HER2蛋白的CAR（ErbB2CAR），该蛋白在HGSOC中过表达，并在卵巢癌细胞系（OVCAR8、SKOV3和NAR）上评估了ErbB2CAR的功能。我们的研究结果表明，与IV途径相比，向荷瘤小鼠IP注射ErbB2CAR-T细胞可导致疾病缓解并提高生存率。此外，我们发现IP注射的ErbB2CAR-T细胞循环程度较低，使其对非肿瘤组织比IV注射的细胞更安全。进一步支持我们的发现，我们表明ErbB2CAR-T细胞对原发性HGSOC肿瘤的效果与ErbB2表达相关。总之，这些数据表明IP给予CAR-T细胞优于IV给药，不仅提供了一种更安全的策略，还具有抵消ErbB2CAR在HGSOC中效果的潜力。意义：与IV途径相比，IP注射的ErbB2CAR-T细胞导致疾病缓解并增加生存率。这些发现证明了IP给药的优势，提供了一种安全的治疗策略，并具有抵消ErbB2CAR在HGSOC中效果的潜力。
High-grade serous ovarian carcinoma (HGSOC) is the most common type of epithelial ovarian cancer. The majority of cases are diagnosed at advanced stages, when intraperitoneal (IP) spread has already occurred. Despite significant surgical and chemotherapeutic advances in HGSOC treatment over the past decades, survival rates with HGSOC have only modestly improved. Chimeric antigen receptor (CAR)-T cells enable T cells to directly bind to tumor-associated antigens in a major histocompatibility complex-independent manner, thereby inducing tumor rejection. While CAR-T cell therapy shows great promise in hematological malignancies, its use in solid tumors is limited. Therefore, innovative approaches are needed to increase the specificity of CAR-modified T cells against solid tumors. The aim of this study was to assess the efficacy and safety of intraperitoneal (IP) versus intravenous (IV) CAR-T cell therapy in the treatment of HGSOC. We constructed a CAR that targets the ErbB2/HER2 protein (ErbB2CAR), which is overexpressed in HGSOC, and evaluated the functionality of ErbB2CAR on ovarian cancer cell lines (OVCAR8, SKOV3, and NAR). Our findings show that an IP injection of ErbB2CAR-T cells to tumor-bearing mice led to disease remission and increased survival compared to the IV route. Moreover, we found that IP-injected ErbB2CART cells circulate to a lesser extent, making them safer for non-tumor tissues than IV-injected cells. Further supporting our findings, we show that the effect of ErbB2CAR-T cells on primary HGSOC tumors is correlated with ErbB2 expression. Together, these data demonstrate the advantages of an IP administration of CAR-T cells over IV administration, offering not only a safer strategy but also the potential for counteracting the effect of ErbB2CAR in HGSOC. Significance: IP-injected ErbB2CAR-T cells led to disease remission and increased survival compared to the IV route. These findings demonstrate the advantages of IP administration, offering a safe treatment strategy with the potential for counteracting the effect of ErbB2CAR in HGSOC.
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