肿瘤细胞治疗研究
英文原题：Next-generation T cell engagers for cancer and autoimmune diseases.
Next-generation T cell engagers for cancer and autoimmune diseases.
T细胞衔接抗体构建体（TCEs）已成为治疗癌症和自身免疫性疾病的一种有效手段。
T 细胞衔接抗体构建体（TCE）已成为治疗癌症和自身免疫性疾病的一种有效手段。已有 12 种 TCE 获得 FDA 和 EMA 批准，用于治疗血液系统恶性肿瘤或实体瘤。尽管设计各异、结合特性不同，它们均能产生稳健的单药疗效，并获批用于难治性或复发性白血病、淋巴瘤、多发性骨髓瘤（MM）、小细胞肺癌、表达 EpCAM 的癌症或葡萄膜黑色素瘤。在可推断比较的情况下，TCE 似乎可达到与 CAR-T 细胞疗法相似的缓解率。鉴于第一代 TCE 的成功，目前正在进行大量尝试以进一步改进这一治疗模式。为了将 TCE 拓展至其他恶性及自身免疫性适应症，并进一步增强疗效和改善安全性，大量新型 TCE 目前正处于临床前和临床开发阶段。本文综述了当前开发下一代 TCE 的方法，这些方法能够拓宽治疗指数、应对异质性靶点表达，从而可能改善疗效和安全性。
T cell-engaging antibody constructs (TCEs) have emerged as a potent modality to treat cancer and autoimmune diseases. Twelve TCEs have been approved by the FDA and EMA for the treatment of hematological malignancies or solid tumors. Despite the varying designs and binding properties, they all lead to robust single-agent efficacy and approvals in refractory or relapsed leukemia, lymphomas, multiple myeloma (MM), small cell lung cancer, EpCAM-expressing cancers or uveal melanoma. Where comparisons can be deduced, TCEs appear to achieve response rates like those obtained with CAR-T cell therapies. Given the success of the first generation of TCEs, considerable attempts are underway to further improve upon this modality. With the goal of expanding TCEs into other malignant and autoimmune indications, and to further enhance efficacy and improve safety, a multitude of novel TCEs are currently in preclinical and clinical development. Here we review the current approaches to developing next-generation TCEs that can widen the therapeutic index, address heterogeneous target expression, and thereby potentially improve efficacy and safety.
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