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:Strategies to Overcome Hurdles in Cancer Immunotherapy.
这些策略有望提高癌症免疫疗法的疗效,为抗癌治疗开辟新视野。
尽管过去几十年来癌症免疫治疗取得了显著进展,但仍迫切需要开发更有效的人类治疗方法。本综述探讨了克服癌症免疫治疗障碍的策略,利用创新技术,包括多特异性抗体、嵌合抗原受体(CAR)T细胞、髓系细胞、癌症相关成纤维细胞、人工智能(AI)预测的新抗原、自体疫苗和mRNA疫苗。这些方法旨在解决肿瘤免疫逃逸机制的多样性和相互作用。具体而言,多特异性抗体和CAR T细胞增强与肿瘤细胞的相互作用,增强免疫反应以促进肿瘤浸润和破坏。髓系细胞和癌症相关成纤维细胞的调节靶向肿瘤的免疫抑制微环境,增强免疫治疗效果。AI预测的新抗原快速准确地识别抗原靶点,这可以促进个性化抗癌疫苗的开发。此外,自体疫苗和mRNA疫苗激活个体的免疫系统,促进针对癌症新抗原的持久免疫反应,作为治疗性疫苗。总体而言,这些策略有望增强癌症免疫治疗的疗效,为抗癌治疗开辟新视野。
Despite marked advancements in cancer immunotherapy over the past few decades, there remains an urgent need to develop more effective treatments in humans. This review explores strategies to overcome hurdles in cancer immunotherapy, leveraging innovative technologies including multi-specific antibodies, chimeric antigen receptor (CAR) T cells, myeloid cells, cancer-associated fibroblasts, artificial intelligence (AI)-predicted neoantigens, autologous vaccines, and mRNA vaccines. These approaches aim to address the diverse facets and interactions of tumors' immune evasion mechanisms. Specifically, multi-specific antibodies and CAR T cells enhance interactions with tumor cells, bolstering immune responses to facilitate tumor infiltration and destruction. Modulation of myeloid cells and cancer-associated fibroblasts targets the tumor's immunosuppressive microenvironment, enhancing immunotherapy efficacy. AI-predicted neoantigens swiftly and accurately identify antigen targets, which can facilitate the development of personalized anticancer vaccines. Additionally, autologous and mRNA vaccines activate individuals' immune systems, fostering sustained immune responses against cancer neoantigens as therapeutic vaccines. Collectively, these strategies are expected to enhance efficacy of cancer immunotherapy, opening new horizons in anticancer treatment.
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