Intratumoral Immunotherapy-Update 2019
Intratumoral Immunotherapy-Update 2019
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DOI：
10.1634/theoncologist.2019-0438
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发表时间：
2019-11-29
期刊：
影响因子：
5.8
通讯作者：
Puzanov, Igor
中科院分区：
文献类型：
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作者：
Hamid, Omid;Ismail, Rubina;Puzanov, Igor
瘤内免疫疗法旨在通过直接注射免疫刺激剂来触发局部和全身免疫反应，目的是裂解肿瘤细胞，随后释放肿瘤源性抗原并随后激活肿瘤特异性效应T细胞。 2019年，多种具有不同作用机制的瘤内免疫疗法，包括PV-10和Toll样受体9激动剂等非溶瘤病毒疗法，以及CAVATAK、Pexa-Vec和HF10等溶瘤病毒疗法，已在临床试验中得到广泛评估，并在黑色素瘤和其他实体瘤类型中表现出有前景的抗肿瘤活性和可耐受的毒性。 Talimogene laherparepvec (T-VEC) 是一种基于 1 型单纯疱疹病毒的转基因溶瘤免疫疗法，是美国食品和药物管理局批准的第一种溶瘤病毒，用于治疗初次手术后复发的不可切除黑色素瘤。在无法切除的转移性黑色素瘤患者中，T-VEC 表现出优于皮下 GM-CSF 的持久缓解率（持续完全缓解或部分缓解持续 >= 6 个月）（16.3% vs. 2.1%；p < .001）。在注射和未注射的病变（包括内脏病变）中均观察到反应，表明存在全身抗肿瘤反应。与免疫检查点抑制剂联合使用时，T-VEC 较单药显着提高缓解率；检查点抑制剂和其他肿瘤内治疗（例如 CAVATAK、HF10 和 TLR9 激动剂）的组合也得到了类似的结果。在这篇综述中，我们重点介绍了正在临床评估的关键肿瘤内免疫疗法的临床试验的最新结果，重点是 T-VEC 在治疗晚期黑色素瘤中作为未来实体瘤适应症的模型。对实践的影响本综述为肿瘤学家提供了有关关键瘤内免疫疗法（特别是溶瘤病毒）开发的最新信息。目前，T-VEC是唯一获得美国食品和药物管理局（FDA）批准的溶瘤免疫疗法。本文重点介绍了 T-VEC 作为单一疗法以及与免疫检查点抑制剂联合使用的临床试验的有效性和安全性数据。这篇综述总结了肿瘤内治疗的最新知识，肿瘤内治疗是一种在癌症治疗中实用性增强的新型治疗方式，而 T-VEC 是唯一经美国 FDA 批准的溶瘤病毒治疗，供肿瘤内科医师使用。本综述评估了将 T-VEC 纳入日常实践的方法，以便与其他可用的免疫疗法相比，为选定的黑色素瘤患者提供可控制不良事件的缓解可能性。
Intratumoral immunotherapies aim to trigger local and systemic immunologic responses via direct injection of immunostimulatory agents with the goal of tumor cell lysis, followed by release of tumor-derived antigens and subsequent activation of tumor-specific effector T cells. In 2019, a multitude of intratumoral immunotherapies with varied mechanisms of action, including nononcolytic viral therapies such as PV-10 and toll-like receptor 9 agonists and oncolytic viral therapies such as CAVATAK, Pexa-Vec, and HF10, have been extensively evaluated in clinical trials and demonstrated promising antitumor activity with tolerable toxicities in melanoma and other solid tumor types. Talimogene laherparepvec (T-VEC), a genetically modified herpes simplex virus type 1-based oncolytic immunotherapy, is the first oncolytic virus approved by the U.S. Food and Drug Administration for the treatment of unresectable melanoma recurrent after initial surgery. In patients with unresectable metastatic melanoma, T-VEC demonstrated a superior durable response rate (continuous complete response or partial response lasting >= 6 months) over subcutaneous GM-CSF (16.3% vs. 2.1%; p < .001). Responses were seen in both injected and uninjected lesions including visceral lesions, suggesting a systemic antitumor response. When combined with immune checkpoint inhibitors, T-VEC significantly improved response rates compared with single agent; similar results were seen with combinations of checkpoint inhibitors and other intratumoral therapies such as CAVATAK, HF10, and TLR9 agonists. In this review, we highlight recent results from clinical trials of key intratumoral immunotherapies that are being evaluated in the clinic, with a focus on T-VEC in the treatment of advanced melanoma as a model for future solid tumor indications. Implications for Practice This review provides oncologists with the latest information on the development of key intratumoral immunotherapies, particularly oncolytic viruses. Currently, T-VEC is the only U.S. Food and Drug Administration (FDA)-approved oncolytic immunotherapy. This article highlights the efficacy and safety data from clinical trials of T-VEC both as monotherapy and in combination with immune checkpoint inhibitors. This review summarizes current knowledge on intratumoral therapies, a novel modality with increased utility in cancer treatment, and T-VEC, the only U.S. FDA-approved oncolytic viral therapy, for medical oncologists. This review evaluates approaches to incorporate T-VEC into daily practice to offer the possibility of response in selected melanoma patients with manageable adverse events as compared with other available immunotherapies.