Chang Yun, Chang Mingyang, Bao Xiaoping, Dong Cheng
Department of Biomedical Engineering, The Hong Kong Polytechnic University, 999077, Hong Kong, China.
The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518000, China.
Bioact Mater. 2024 Sep 10;42:379-403. doi: 10.1016/j.bioactmat.2024.08.046. eCollection 2024 Dec.
Adoptive immunotherapy, notably involving chimeric antigen receptor (CAR)-T cells, has obtained Food and Drug Administration (FDA) approval as a treatment for various hematological malignancies, demonstrating promising preclinical efficacy against cancers. However, the intricate and resource-intensive autologous cell processing, encompassing collection, expansion, engineering, isolation, and administration, hamper the efficacy of this therapeutic modality. Furthermore, conventional CAR T therapy is presently confined to addressing solid tumors due to impediments posed by physical barriers, the potential for cytokine release syndrome, and cellular exhaustion induced by the immunosuppressive and heterogeneous tumor microenvironment. Consequently, a strategic integration of adoptive immunotherapy with synergistic multimodal treatments, such as chemotherapy, radiotherapy, and vaccine therapy etc., emerges as a pivotal approach to surmount these inherent challenges. This collaborative strategy holds the key to addressing the limitations delineated above, thereby facilitating the realization of more precise personalized therapies characterized by heightened therapeutic efficacy. Such synergistic strategy not only serves to mitigate the constraints associated with adoptive immunotherapy but also fosters enhanced clinical applicability, thereby advancing the frontiers of therapeutic precision and effectiveness.
过继性免疫疗法,尤其是涉及嵌合抗原受体(CAR)-T细胞的疗法,已获得美国食品药品监督管理局(FDA)批准,可用于治疗多种血液系统恶性肿瘤,显示出对癌症有前景的临床前疗效。然而,复杂且资源密集的自体细胞处理过程,包括采集、扩增、工程改造、分离和给药,阻碍了这种治疗方式的疗效。此外,由于物理屏障造成的阻碍、细胞因子释放综合征的可能性以及免疫抑制和异质性肿瘤微环境诱导的细胞耗竭,传统的CAR-T疗法目前仅限于治疗实体瘤。因此,将过继性免疫疗法与化疗、放疗和疫苗疗法等协同多模态治疗进行战略整合,成为克服这些固有挑战的关键方法。这种协同策略是解决上述局限性的关键,从而有助于实现以更高治疗效果为特征的更精确的个性化治疗。这种协同策略不仅有助于减轻与过继性免疫疗法相关的限制,还能提高临床适用性,从而推进治疗精准度和有效性的前沿。