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:Oncolytic human herpesvirus for cancer therapy.
单纯疱疹病毒(HSV)因其基因容量、对多种肿瘤的作用、触发免疫反应的能力以及对癌症微环境的适应性,在溶瘤治疗中具有吸引力。
单纯疱疹病毒(HSV)因其基因容量、对多种肿瘤的作用、触发免疫反应的能力以及对癌症微环境的适应性,在溶瘤治疗中具有吸引力。通过基因修饰帮助单纯疱疹病毒逃逸适应性免疫并更好地引导免疫反应,可以增强其溶瘤潜力。该病毒在癌细胞中特异性复制,但不伤害正常细胞。肿瘤微环境中的免疫原性细胞死亡和细胞因子释放等效应可阻碍癌症的免疫侵袭并提高治疗效果。溶瘤HSV(oHSV)疗法无论是作为独立治疗还是与免疫检查点抑制剂、CAR-T 细胞疗法和细胞因子联合使用,都显示出巨大潜力。oHSV重塑肿瘤微环境、激活免疫细胞并诱导全身性抗肿瘤免疫反应的能力有助于其整体治疗效果,尤其是在转移性癌症的治疗中。临床前和临床研究表明,基于单纯疱疹病毒的病毒疗法对某些癌症有效,包括黑色素瘤、头颈癌和胶质母细胞瘤。在单纯疱疹病毒中使用个性化元素,如新抗原、肿瘤特异性启动子和趋化因子,为定制化病毒疗法提供了令人振奋的潜力。正在进行的研究和生物技术进步有望产生更安全、更高效的治疗方法,促进oHSV在癌症管理中的更广泛应用。本研究探讨了HSV的肿瘤特异性修饰在癌症治疗中的进展,并讨论了oHSV与其他治疗协同使用的优势、挑战和建议。
Herpes simplex virus (HSV) is attractive for oncolytic therapy due to its genetic capacity, effect on various tumors, ability to trigger immune responses, and adaptation to the cancer microenvironment. Its oncolytic potential can be enhanced by genetic modifications that help Herpes simplex virus escape adaptive immunity and better direct immune responses. While the virus replicates specifically in cancer cells, it does not harm normal cells. Effects like immunogenic cell death and cytokine release in the tumor microenvironment hinder immune invasion of cancer and improve treatment effectiveness. Oncolytic HSV (oHSV) therapy shows great potential both as an independent treatment and when combined with immune checkpoint inhibitors, Chimeric antigen receptor T cell therapies, and cytokines. The capacity of oHSV to remodel the tumor microenvironment, activate immune cells, and induce systemic antitumor immune responses contributes to its overall therapeutic efficacy, particularly in the treatment of metastatic cancers. Pre-clinical and clinical studies indicate that Herpes simplex virus -based virotherapy can be effective for certain cancers, including melanoma, head and neck cancers, and glioblastoma. The use of personalized elements in Herpes simplex virus, like neoantigens, tumor-specific promoters, and chemokines, offers exciting potential for tailored virotherapy. Ongoing research and biotechnological advances are expected to produce safer, more efficient treatments, fostering wider adoption of oHSV in cancer management. This study examines tumor-specific modifications of HSV advances in cancer therapies, and discusses the benefits, challenges, and recommendations for synergizing oHSV with other treatments.
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