Talimogene laherparepvec和新型注射溶瘤病毒在转移性黑色素瘤治疗中的作用

Frances G. Jenkins, J.E. Johnson, F. Collichio, D. Ollila
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摘要

T-VEC (Talimogene laherparepvec, T-VEC)是一种溶瘤病毒(OV)疗法,衍生自单纯疱疹病毒JS1株,于2015年获得美国食品和药物管理局批准,可作为黑色素瘤患者的直接注射治疗药物。T- vec的抗肿瘤作用是由于给药部位的病毒介导的肿瘤细胞裂解和局部的,在某些情况下,通过GM-CSF辅助的T细胞介导的宿主免疫反应途径产生全身的抗肿瘤反应。T-VEC在转移性黑色素瘤治疗中显示出良好的效果,特别是在皮肤、淋巴结和软组织转移(IIIB、IIIC和IVa期)的患者中。研究已经探索了T-VEC作为单一疗法、新辅助疗法以及与其他免疫疗法和靶向疗法联合使用的效用。T-VEC已被证明可以提高持久的反应率和总体生存率,并具有非常可容忍的安全性。需要更多的研究来更好地了解哪些患者最有可能从T-VEC治疗中获益,哪种联合治疗最有效,以及如何对多模式治疗进行排序。此外,新的OVs目前正在开发和/或正在临床试验中进行研究。在这篇综述中,我们将讨论T-VEC作为单一治疗,新辅助治疗和联合治疗,以及黑色素瘤治疗的未来方向,因为它与新的OVs有关。招募患者的无进展生存期更长。预计完工日期为2022年1月。最后,一项非随机、开放标签、多中心1b/2期试验(MASTERKEY-318)正在评估肿瘤内T-VEC作为单药治疗或联合派姆单抗[43]治疗肝脏肿瘤的疗效和安全性。该研究涉及两组患者,根据潜在疾病进行区分。A组将包括非肝细胞癌(HCC)肝转移患者,包括黑色素瘤。B组包括HCC患者。该研究目前正在招募患者,预计完成日期为2022年10月25日。
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Talimogene laherparepvec and novel injectable oncolytic viruses in the management of metastatic melanoma
and viruses Abstract Talimogene laherparepvec (T-VEC) is an oncolytic virus (OV) therapy derived from the JS1 strain of herpes simplex virus one that was approved by the Food and Drug Administration in 2015 to be administered as direct injection therapy for patients with melanoma. The anti-tumor effects of T-VEC are due to viral-mediated tumor cell lysis at the site of administration and a local, and in some cases systemic, anti-tumor response via T cell-mediated host immune response pathways aided by GM-CSF. T-VEC has shown promising results for metastatic melanoma, particularly in patients with skin, lymph node, and soft tissue metastases (stages IIIB, IIIC, and IVa). Studies have explored the utility of T-VEC as monotherapy, neoadjuvant therapy, and in combination with other immunotherapies and targeted therapies. T-VEC has proven to improve durable response rates and overall survival with a very tolerable safety profile. More research is needed to better understand which patients are most likely to benefit from T-VEC therapy, which combination therapies are most effective, and how to sequence multimodality therapy. Additionally, new OVs are currently in development and/or being studied in clinical trials. In this review, we will discuss T-VEC as a monotherapy, neoadjuvant therapy, and combination therapy, in addition to future directions for melanoma therapy as it pertains to new OVs. progression-free survival longer recruiting patients. The estimated completion date is in January 2022. Finally, a non-randomized, open-label, multicenter phase 1b/2 trial (MASTERKEY-318) is assessing the efficacy and safety of intratumoral T-VEC in liver tumors as either monotherapy or in combination with pembrolizumab [43] . The study involves two groups of patients, distinguished based on the underlying disease. Group A will involve patients with non-hepatocellular carcinoma (HCC) liver metastases, including melanoma. Group B will include patients with HCC. This study is currently recruiting patients and has an estimated completion date of October 25, 2022.
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