决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Immunotherapeutics in metastatic cancer management.
转移性癌症仍然是癌症相关死亡的主要原因,这在很大程度上归因于化疗、放疗和靶向药物等传统治疗的局限性,这些治疗受到肿瘤异质性、获得性耐药和全身毒性的挑战。
转移性癌症仍然是癌症相关死亡的主要原因,这在很大程度上归因于传统治疗方法的局限性,如化疗、放疗和靶向药物,这些方法面临肿瘤异质性、获得性耐药和全身毒性的挑战。相比之下,免疫治疗已成为一种变革性治疗模式,利用免疫系统的力量选择性靶向并根除肿瘤细胞。本综述系统考察了关键免疫治疗策略,从免疫检查点抑制剂(ICIs)和单克隆抗体到癌症疫苗、溶瘤病毒和过继细胞疗法(如CAR-T和TCR工程化T细胞)。尤其值得关注的是个性化方法,包括基于新抗原的疫苗和TIL(肿瘤浸润淋巴细胞)疗法,这些方法有望实现量身定制的治疗,但也面临重大的物流和转化挑战。治疗结局的核心因素包括免疫抵抗、抑制性肿瘤微环境,以及预测性生物标志物的识别,包括PD-L1表达和肿瘤突变负荷(TMB),可用于指导患者选择和疗效评估。随着该领域的进展,未来的突破将取决于深化我们对转移免疫生物学的理解、完善生物标志物驱动的精准方法,以及开发新的免疫靶点和递送平台以改善结局和可及性。
Metastatic cancer remains the leading cause of cancer-related mortality, largely owing to the limitations of conventional treatments such as chemotherapy, radiotherapy, and targeted agents that are challenged by tumor heterogeneity, acquired resistance, and systemic toxicity. In contrast, immunotherapy has emerged as a transformative modality, harnessing the power of the immune system to selectively target and eradicate tumor cells. This review systematically examines key immunotherapeutic strategies ranging from immune checkpoint inhibitors (ICIs) and monoclonal antibodies to cancer vaccines, oncolytic viruses, and adoptive cell therapies (such as CAR-T and TCR-engineered T cells). Of particular interest are personalized approaches, including neoantigen-based vaccines and tumor-infiltrating lymphocyte (TIL) therapies, which hold promise for tailored treatment but also present significant logistical and translational challenges. Central to therapeutic outcomes are factors like immune resistance, the suppressive tumor microenvironment, and the identification of predictive biomarkers including PD-L1 expression and tumor mutational burden (TMB) that can guide patient selection and efficacy. As the field progresses, future breakthroughs will hinge on deepening our understanding of metastasis immunobiology, refining biomarker-driven precision approaches, and developing novel immunological targets and delivery platforms to improve outcomes and accessibility.
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