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:New hopes for the breast cancer treatment: perspectives on the oncolytic virus therapy.
溶瘤病毒(OV)疗法已成为癌症治疗中一个有前景的前沿方向,尤其是针对实体瘤。
溶瘤病毒(OV)疗法已成为癌症治疗(尤其是实体瘤)的有前景新方向。尽管免疫检查点抑制剂和CAR-T细胞等免疫疗法已取得显著成果,但其诱导肿瘤完全消退的能力有限,促使研究者探索针对现有免疫疗法耐药肿瘤的新方法。天然或基因工程改造的OV可选择性地在癌细胞内复制并诱导其裂解,同时保护正常组织。近期临床研究和基因工程进展推动开发靶向性病毒,这些病毒可改变肿瘤微环境、触发抗肿瘤免疫应答,并与其他癌症疗法产生协同作用。已有多种OV用于乳腺癌治疗研究,包括腺病毒、原细小病毒、痘苗病毒、呼肠孤病毒和单纯疱疹病毒1型(HSV-1)。这些病毒经过改造或工程化,以增强肿瘤选择性复制、降低毒性并改善溶瘤特性。新一代OV(如Oncoviron和Delta-24-RGD腺病毒)具有更高的复制选择性和更强的抗癌作用,尤其在乳腺癌模型中。临床试验已研究多种OV治疗黑色素瘤、鼻咽癌、头颈部癌及妇科恶性肿瘤的疗效和安全性。值得注意的是,Talimogene laherparepvec(T-VEC)和Oncorine已分别获批用于晚期黑色素瘤和鼻咽癌。但部分病例报告了不良反应,包括流感样症状,以及少见的瘘管形成等严重并发症。尽管目前尚无OV获批专门用于乳腺癌治疗,正在进行的临床前和临床试验聚焦于四类病毒。虽然观察到低热和恶心等轻度不良反应,OV单药治疗乳腺癌的疗效仍不足。将OV与化疗、放疗或免疫治疗联合的策略有望改善治疗结局。OV疗法在乳腺癌治疗中潜力巨大,且试验中显示出安全性。与单药治疗相比,OV联合常规疗法的多模式策略显示出更有希望的治疗效果,预示着OV乳腺癌治疗的良好前景。
Oncolytic virus (OV) therapy has emerged as a promising frontier in cancer treatment, especially for solid tumours. While immunotherapies like immune checkpoint inhibitors and CAR-T cells have demonstrated impressive results, their limitations in inducing complete tumour regression have spurred researchers to explore new approaches targeting tumours resistant to current immunotherapies. OVs, both natural and genetically engineered, selectively replicate within cancer cells, inducing their lysis while sparing normal tissues. Recent advancements in clinical research and genetic engineering have enabled the development of targeted viruses that modify the tumour microenvironment, triggering anti-tumour immune responses and exhibiting synergistic effects with other cancer therapies. Several OVs have been studied for breast cancer treatment, including adenovirus, protoparvovirus, vaccinia virus, reovirus, and herpes simplex virus type I (HSV-1). These viruses have been modified or engineered to enhance their tumour-selective replication, reduce toxicity, and improve oncolytic properties.Newer generations of OVs, such as Oncoviron and Delta-24-RGD adenovirus, exhibit heightened replication selectivity and enhanced anticancer effects, particularly in breast cancer models. Clinical trials have explored the efficacy and safety of various OVs in treating different cancers, including melanoma, nasopharyngeal carcinoma, head and neck cancer, and gynecologic malignancies. Notably, Talimogene laherparepvec (T-VEC) and Oncorine have. been approved for advanced melanoma and nasopharyngeal carcinoma, respectively. However, adverse effects have been reported in some cases, including flu-like symptoms and rare instances of severe complications such as fistula formation. Although no OV has been approved specifically for breast cancer treatment, ongoing preclinical clinical trials focus on four groups of viruses. While mild adverse effects like low-grade fever and nausea have been observed, the effectiveness of OV monotherapy in breast cancer remains insufficient. Combination strategies integrating OVs with chemotherapy, radiotherapy, or immunotherapy, show promise in improving therapeutic outcomes. Oncolytic virus therapy holds substantial potential in breast cancer treatment, demonstrating safety in trials. Multi-approach strategies combining OVs with conventional therapies exhibit more promising therapeutic effects than monotherapy, signalling a hopeful future for OV-based breast cancer treatments.
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