通过靶向肿瘤相关巨噬细胞的嵌合受体工程化溶瘤病毒重振内源性抗肿瘤免疫
Rejuvenating endogenous antitumor immunity via a chimeric receptor-engineered oncolytic virus targeting tumor-associated macrophages.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Engineering strategies to enhance oncolytic viruses in cancer immunotherapy.
Engineering strategies to enhance oncolytic viruses in cancer immunotherapy.
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溶瘤病毒(OVs)正逐渐成为治疗肿瘤患者的一种潜在有用平台。它们优先靶向并杀死肿瘤细胞,而不伤害健康细胞。除了直接溶瘤作用外,溶瘤病毒治疗的重要且吸引人的方面还基于其内在诱导先天性和适应性免疫应答的能力。为了进一步增强这种有效应答,OVs已被基因工程改造以表达增强或恢复抗肿瘤免疫的免疫调节因子。最近,OVs与其他免疫疗法(如免疫检查点抑制剂(ICIs)、嵌合抗原受体(CARs)、抗原特异性T细胞受体(TCRs)和自体TIL(肿瘤浸润淋巴细胞)(TILs))的联合治疗已在癌症治疗中取得了有希望的进展。本综述总结了OVs的内在机制,描述了使用武装OVs增强抗肿瘤免疫效应的优化策略,并重点介绍了近期临床前和临床研究中OVs与其他免疫疗法的合理联合。
Oncolytic viruses (OVs) are emerging as potentially useful platforms in treatment methods for patients with tumors. They preferentially target and kill tumor cells, leaving healthy cells unharmed.
In addition to direct oncolysis, the essential and attractive aspect of oncolytic virotherapy is based on the intrinsic induction of both innate and adaptive immune responses. To further augment this efficacious response, OVs have been genetically engineered to express immune regulators that enhance or restore antitumor immunity.
Recently, combinations of OVs with other immunotherapies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptors (CARs), antigen-specific T-cell receptors (TCRs) and autologous tumor-infiltrating lymphocytes (TILs), have led to promising progress in cancer treatment. This review summarizes the intrinsic mechanisms of OVs, describes the optimization strategies for using armed OVs to enhance the effects of antitumor immunity and highlights rational combinations of OVs with other immunotherapies in recent preclinical and clinical studies.
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