Han Jia, Zhang Bowen, Zheng Senyu, Jiang Yuan, Zhang Xiaopeng, Mao Kaiyun
Shanghai Information Center for Life Sciences, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, Shanghai, China.
School of Natural and Computing Sciences, University of Aberdeen, Aberdeen, UK.
Cell Transplant. 2024 Jan-Dec;33:9636897241231892. doi: 10.1177/09636897241231892.
Immune cell therapy as a revolutionary treatment modality, significantly transformed cancer care. It is a specialized form of immunotherapy that utilizes living immune cells as therapeutic reagents for the treatment of cancer. Unlike traditional drugs, cell therapies are considered "living drugs," and these products are currently customized and require advanced manufacturing techniques. Although chimeric antigen receptor (CAR)-T cell therapies have received tremendous attention in the industry regarding the treatment of hematologic malignancies, their effectiveness in treating solid tumors is often restricted, leading to the emergence of alternative immune cell therapies. Tumor-infiltrating lymphocytes (TIL) cell therapy, cytokine-induced killer (CIK) cell therapy, dendritic cell (DC) vaccines, and DC/CIK cell therapy are designed to use the body's natural defense mechanisms to target and eliminate cancer cells, and usually have fewer side effects or risks. On the other hand, cell therapies, such as chimeric antigen receptor-T (CAR-T) cell, T cell receptor (TCR)-T, chimeric antigen receptor-natural killer (CAR-NK), or CAR-macrophages (CAR-M) typically utilize either autologous stem cells, allogeneic or xenogeneic cells, or genetically modified cells, which require higher levels of manipulation and are considered high risk. These high-risk cell therapies typically hold special characteristics in tumor targeting and signal transduction, triggering new anti-tumor immune responses. Recently, significant advances have been achieved in both basic and clinical researches on anti-tumor mechanisms, cell therapy product designs, and technological innovations. With swift technological integration and a high innovation landscape, key future development directions have emerged. To meet the demands of cell therapy technological advancements in treating cancer, we comprehensively and systematically investigate the technological innovation and clinical progress of immune cell therapies in this study. Based on the therapeutic mechanisms and methodological features of immune cell therapies, we analyzed the main technical advantages and clinical transformation risks associated with these therapies. We also analyzed and forecasted the application prospects, providing references for relevant enterprises with the necessary information to make informed decisions regarding their R&D direction selection.
免疫细胞疗法作为一种革命性的治疗方式,显著改变了癌症治疗模式。它是免疫疗法的一种特殊形式,利用活的免疫细胞作为治疗癌症的试剂。与传统药物不同,细胞疗法被视为“活药物”,并且这些产品目前是定制的,需要先进的制造技术。尽管嵌合抗原受体(CAR)-T细胞疗法在血液系统恶性肿瘤治疗方面已在业内受到极大关注,但其在治疗实体瘤方面的有效性往往受到限制,从而催生了替代免疫细胞疗法。肿瘤浸润淋巴细胞(TIL)细胞疗法、细胞因子诱导的杀伤细胞(CIK)疗法、树突状细胞(DC)疫苗以及DC/CIK细胞疗法旨在利用人体的天然防御机制来靶向和消除癌细胞,并且通常副作用或风险较少。另一方面,诸如嵌合抗原受体-T(CAR-T)细胞、T细胞受体(TCR)-T、嵌合抗原受体-自然杀伤细胞(CAR-NK)或CAR-巨噬细胞(CAR-M)等细胞疗法通常利用自体干细胞、同种异体或异种细胞,或者基因改造细胞,这些需要更高水平的操作且被认为具有高风险。这些高风险细胞疗法通常在肿瘤靶向和信号转导方面具有特殊特征,引发新的抗肿瘤免疫反应。最近,在抗肿瘤机制、细胞治疗产品设计和技术创新的基础研究和临床研究方面均取得了重大进展。随着技术的迅速整合和高度创新局面的出现,关键的未来发展方向已经显现。为了满足细胞疗法技术进步在癌症治疗方面的需求,我们在本研究中全面系统地调查了免疫细胞疗法的技术创新和临床进展。基于免疫细胞疗法的治疗机制和方法学特征,我们分析了与这些疗法相关的主要技术优势和临床转化风险。我们还分析并预测了应用前景,为相关企业提供参考信息,以便它们在研发方向选择上做出明智决策。