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:Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner.
Harnessing adenovirus in cancer immunotherapy: evoking cellular immunity and targeting delivery in cell-specific manner.
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重组腺病毒(rAd)方案,包括复制 competent 溶瘤腺病毒(OAV)和复制缺陷型腺病毒,已被确定为潜在的癌症治疗手段。OAV 具有选择性复制、溶瘤效果和肿瘤微环境(TME)重塑等优势。
在此视角下,综述了开发 OAV 工具包的原则和进展。新兴的 rAd 可能决定常规癌症疗法以及癌症免疫疗法的疗效,包括癌症疫苗、与过继细胞疗法(ACT)的协同作用以及 TME 重塑。
同时,我们探讨了 rAd 搭乘过继免疫细胞或干细胞的潜力,强调了这种方法如何促进 rAd 与细胞疗法在肿瘤部位的协同相互作用。免疫细胞和干细胞被 rAd 感染的临床前和临床试验结果已被用于解决重大的肿瘤学挑战,例如术后残留肿瘤组织和转移组织。简而言之,rAd 可以通过多种机制根除肿瘤,这些机制源于肿瘤免疫原性、TME 重编程、细胞免疫增强和有效的肿瘤靶向。
在此背景下,我们认为 rAd 在增强细胞免疫和与新型癌症免疫疗法联合协同改善抗肿瘤效果方面具有巨大潜力。
Recombinant adenovirus (rAd) regimens, including replication-competent oncolytic adenovirus (OAV) and replication-deficient adenovirus, have been identified as potential cancer therapeutics. OAV presents advantages such as selective replication, oncolytic efficacy, and tumor microenvironment (TME) remodeling. In this perspective, the principles and advancements in developing OAV toolkits are reviewed. The burgeoning rAd may dictate efficacy of conventional cancer therapies as well as cancer immunotherapies, including cancer vaccines, synergy with adoptive cell therapy (ACT), and TME reshaping. Concurrently, we explored the potential of rAd hitchhiking to adoptive immune cells or stem cells, highlighting how this approach facilitates synergistic interactions between rAd and cellular therapeutics at tumor sites.
Results from preclinical and clinical trials in which immune and stem cells were infected with rAd have been used to address significant oncological challenges, such as postsurgical residual tumor tissue and metastatic tissue.
Briefly, rAd can eradicate tumors through various mechanisms, resulting from tumor immunogenicity, reprogramming of the TME, enhancement of cellular immunity, and effective tumor targeting. In this context, we argue that rAd holds immense potential for enhancing cellular immunity and synergistically improving antitumor effects in combination with novel cancer immunotherapies.
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