Bommareddy Praveen K, Silk Ann W, Kaufman Howard L
From the Departments of *Surgery and †Medicine, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ.
Cancer J. 2017 Jan/Feb;23(1):40-47. doi: 10.1097/PPO.0000000000000234.
There have been significant advances in the immunotherapy of melanoma over the last decade. The tumor microenvironment is now known to promote an immune-suppressive milieu that can block effective immune-mediated tumor rejection. Several novel strategies designed to overcome local immunosuppression hold promise for treatment of melanoma and other cancers. These approaches include oncolytic viruses, plasmid DNA delivery, Toll-like receptor agonists, inflammatory dyes, cytokines, checkpoint inhibitors, immunomodulatory agents, and host and pathogenic cell-based vectors. In addition, there are several novel methods for local drug delivery, including direct injection, image-guided, electroporation, and nanodelivery techniques under study. The approval of talimogene laherparepvec (Imlygic), an attenuated, recombinant oncolytic herpesvirus, for melanoma treatment is the first intratumoral agent to receive regulatory approval for the treatment of patients with melanoma. This review will focus on the rationale for intratumoral treatment in melanoma, describe the clinical and safety data for some of the agents in clinical development, and provide a perspective for future clinical investigation with intratumoral approaches. Melanoma has been a paradigm tumor for progress in targeted therapy and immunotherapy and will likely also be the tumor to establish the therapeutic role of intratumoral treatment for cancer.
在过去十年中，黑色素瘤的免疫治疗取得了重大进展。现在已知肿瘤微环境会促进免疫抑制环境，从而阻碍有效的免疫介导肿瘤排斥反应。旨在克服局部免疫抑制的几种新策略有望用于治疗黑色素瘤和其他癌症。这些方法包括溶瘤病毒、质粒DNA递送、Toll样受体激动剂、炎性染料、细胞因子、检查点抑制剂、免疫调节剂以及基于宿主和致病细胞的载体。此外，还有几种局部给药的新方法，包括正在研究的直接注射、图像引导、电穿孔和纳米递送技术。减毒重组溶瘤疱疹病毒塔利莫基因拉赫帕里韦克（Imlygic）获批用于黑色素瘤治疗，这是首个获得监管批准用于治疗黑色素瘤患者的瘤内治疗药物。本综述将重点关注黑色素瘤瘤内治疗的基本原理，描述一些处于临床开发阶段药物的临床和安全性数据，并为未来瘤内治疗方法的临床研究提供一个视角。黑色素瘤一直是靶向治疗和免疫治疗进展的典型肿瘤，也可能会成为确立瘤内治疗对癌症治疗作用的肿瘤。
