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:Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response.
癌症是高度复杂的疾病,其特征不仅在于恶性细胞的过度生长,还在于免疫反应的改变。
癌症是高度复杂的疾病,其特征不仅是恶性细胞的过度生长,还包括免疫反应的改变。免疫系统的抑制和重编程在肿瘤的发生和进展中起着关键作用。免疫治疗旨在重新激活抗肿瘤免疫细胞并克服肿瘤的免疫逃逸机制。以免疫检查点阻断和过继性细胞转移为代表的肿瘤免疫治疗已在临床上取得了巨大成功,能够诱导一些对其他所有治疗均难治的肿瘤长期消退。其中,以PD-1/PD-L1抑制剂(nivolumab)和CTLA-4抑制剂(ipilimumab)为代表的免疫检查点阻断治疗,在多种恶性肿瘤的治疗中显示出令人鼓舞的疗效,如非小细胞肺癌(NSCLC)和黑色素瘤。此外,随着CAR-T、CAR-M等新型免疫治疗方法的出现,免疫治疗已进入新时代。目前,有证据表明,多种免疫治疗方法的联合可能是提高治疗效果的一种途径。然而,肿瘤免疫治疗的整体临床反应率仍有待提高,这就需要开发新的治疗设计以及发现能够指导这些药物处方的生物标志物。从临床和基础研究过去的成功与失败中学习,对于未来研究的合理设计至关重要。在本文中,我们描述了操纵免疫系统对抗癌症的努力,并讨论了可用于促进抗肿瘤免疫反应的不同靶点和细胞类型。
Cancers are highly complex diseases that are characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming of the immune system play critical roles in tumor initiation and progression. Immunotherapy aims to reactivate antitumor immune cells and overcome the immune escape mechanisms of tumors. Represented by immune checkpoint blockade and adoptive cell transfer, tumor immunotherapy has seen tremendous success in the clinic, with the capability to induce long-term regression of some tumors that are refractory to all other treatments. Among them, immune checkpoint blocking therapy, represented by PD-1/PD-L1 inhibitors (nivolumab) and CTLA-4 inhibitors (ipilimumab), has shown encouraging therapeutic effects in the treatment of various malignant tumors, such as non-small cell lung cancer (NSCLC) and melanoma. In addition, with the advent of CAR-T, CAR-M and other novel immunotherapy methods, immunotherapy has entered a new era. At present, evidence indicates that the combination of multiple immunotherapy methods may be one way to improve the therapeutic effect. However, the overall clinical response rate of tumor immunotherapy still needs improvement, which warrants the development of novel therapeutic designs as well as the discovery of biomarkers that can guide the prescription of these agents. Learning from the past success and failure of both clinical and basic research is critical for the rational design of studies in the future. In this article, we describe the efforts to manipulate the immune system against cancer and discuss different targets and cell types that can be exploited to promote the antitumor immune response.
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