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:Novel applications of gene and cell therapies in the treatment of gynecological disorders.
妇科疾病,如宫颈和卵巢肿瘤、子宫肌瘤和子宫内膜异位症,由于频繁复发、新出现的化疗耐药性以及长期激素治疗带来的不良影响,构成了重大的临床挑战。
宫颈癌、卵巢肿瘤、子宫肌瘤和子宫内膜异位症等妇科疾病,常因频繁复发、出现化疗耐药以及长期激素治疗带来的不良影响而构成重大临床挑战。随着肿瘤通过肿瘤抑制基因失活、免疫逃逸和致癌信号通路激活等机制产生耐药,传统治疗往往会逐渐失效。这些局限凸显了开发更精准、持久治疗策略的迫切需求。基因和细胞疗法已成为应对这些挑战的有前景的新一代方法。研究者正在采用CRISPR/Cas9编辑、RNA调控及靶向基因调节,沉默耐药基因、恢复肿瘤抑制因子,并使肿瘤重新对铂类化疗、激素治疗和免疫疗法敏感。受体靶向脂质纳米颗粒(LNP)和病毒载体(VV)等递送平台可增强组织特异性并提高治疗效果。与此同时,改造自然杀伤(NK)细胞和CAR-T细胞等先进免疫细胞疗法正在开发中,旨在清除能够逃避标准治疗的肿瘤克隆。对于良性妇科疾病,间充质干细胞(MSC)具有再生潜力,或可替代反复手术或长期激素抑制治疗。本综述总结子宫疾病和妇科癌症基因与细胞疗法的近期趋势,重点介绍其提高疗效、克服耐药及保护生殖健康的潜力。
Gynecologic disorders, such as cervical and ovarian tumors, uterine fibroids, and endometriosis, present significant clinical challenges due to frequent recurrence, emerging chemoresistance, and undesirable effects associated with prolonged hormonal treatments. Conventional therapies often fail over time as tumors develop resistance through mechanisms that include the inactivation of tumor suppressor genes, immune evasion, and activation of oncogenic signaling pathways. These limitations underscore the urgent need for more precise and durable therapeutic strategies. Gene- and cell-based therapies have emerged as promising next-generation approaches to address these challenges. CRISPR/Cas9-based editing, RNA-directed regulation, and targeted gene modulation are being employed to silence resistance genes, restore tumor suppressors, and resensitize tumors to platinum (Pt)-based chemotherapy, hormonal therapy, and immunotherapy. Delivery platforms such as receptor-targeted lipid nanoparticles (LNPs) and viral vectors (VVs) enhance tissue specificity and improve therapeutic efficacy. Concurrently, advanced immune cell therapies, including modified natural killer (NK) cells and CAR-T cells, are being designed to eradicate tumor clones that evade standard therapeutic approaches. For benign gynecologic conditions, mesenchymal stem cells (MSCs) demonstrate regenerative potential and may offer an alternative to repeated surgical interventions or prolonged hormonal suppression. This review summarizes recent trends in gene and cell therapies for uterine disorders and gynecologic cancers, with a focus on their potential to enhance therapeutic efficacy, overcome drug resistance, and preserve reproductive health.
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