Division of Medical Oncology, Department of Medicine, Washington University in Saint Louis, Saint Louis, MO 63110, USA.
UMKC School of Medicine, University of Missouri Kansas City, Kansas City, MO 64108, USA.
Int J Mol Sci. 2024 Sep 12;25(18):9848. doi: 10.3390/ijms25189848.
Malignant melanoma outcomes have drastically changed in recent years due to the introduction of immune checkpoint inhibitors (ICIs). However, many patients still experience intolerable side effects, therapy resistance, and disease progression on ICI therapy. Therefore, there remains a need for novel therapeutics that address this gap in treatment options. Cell-based therapies have gained wide attention as a therapeutic option that could address this gap in treatment options for advanced melanoma. These therapies work by extracting certain cell types produced in the human body such as T-cells, modifying them based on a specific target, and transfusing them back into the patient. In the realm of cancer therapy, cell-based therapies utilize immune cells to target tumor cells while sparing healthy cells. Recently, the Food and Drug Administration (FDA) has approved the usage of lifileucel, a tumor-infiltrating lymphocyte (TIL) therapy, in advanced melanoma. This came following recent results from the C-144-01 study (NCT02360579), which demonstrated the efficacy and safety of TILs in metastatic melanoma patients who otherwise failed on standard ICI/targeted therapy. Thus, the results of this trial as well as the recent FDA approval have proven the viability of utilizing cell-based therapies to fill the gap in treatment options for patients with advanced melanoma. This review aims to provide a comprehensive overview of major cell-based therapies that have been utilized in melanoma by delineating results of the most recent multi-center phase II/ III clinical trials that evaluate the efficacy and safety of major cell-based therapies in melanoma. Additionally, we provide a summary of current limitations in each cell-based therapeutic option as well as a future direction of how to further extrapolate these cell-based therapies in advanced melanoma.
近年来，由于免疫检查点抑制剂（ICIs）的引入，恶性黑色素瘤的治疗结果发生了巨大变化。然而，许多患者在接受ICI 治疗时仍会经历无法耐受的副作用、治疗抵抗和疾病进展。因此，仍需要新的治疗方法来填补治疗选择的空白。
基于细胞的治疗作为一种治疗选择已经引起了广泛的关注，它可以填补晚期黑色素瘤治疗选择的空白。这些疗法通过提取人体产生的某些细胞类型，如 T 细胞，根据特定目标对其进行修饰，并将其重新注入患者体内来发挥作用。在癌症治疗领域，基于细胞的疗法利用免疫细胞靶向肿瘤细胞，同时保护健康细胞。最近，食品和药物管理局（FDA）批准了 lifileucel（肿瘤浸润淋巴细胞[TIL]疗法）在晚期黑色素瘤中的应用。这是在 C-144-01 研究（NCT02360579）的最新结果之后做出的，该研究表明，在标准 ICI/靶向治疗失败的转移性黑色素瘤患者中，TIL 具有疗效和安全性。因此，该试验的结果以及最近 FDA 的批准证明了利用基于细胞的疗法为晚期黑色素瘤患者填补治疗选择空白的可行性。
本综述旨在通过描述最近的多中心 II/III 期临床试验的结果，为黑色素瘤中已应用的主要基于细胞的疗法提供全面概述，评估主要基于细胞的疗法在黑色素瘤中的疗效和安全性。此外，我们还总结了每种基于细胞的治疗方法的当前局限性，并提出了如何进一步在晚期黑色素瘤中推广这些基于细胞的疗法的未来方向。
