免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Recent Advancements in Cell-Based Therapies in Melanoma.
Recent Advancements in Cell-Based Therapies in Melanoma.
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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局发生了巨大变化。然而,许多患者仍然经历无法耐受的副作用、治疗耐药以及ICI治疗中的疾病进展。
因此,仍然需要新型治疗手段来填补这一治疗选择上的空白。细胞疗法作为一种可能填补晚期黑色素瘤治疗选择空白的治疗选项,已受到广泛关注。这些疗法通过提取人体内产生的某些细胞类型(如T细胞),基于特定靶点对其进行改造,然后将其回输到患者体内。在癌症治疗领域,细胞疗法利用免疫细胞靶向肿瘤细胞,同时不损伤健康细胞。最近,美国食品药品监督管理局(FDA)已批准lifileucel——一种TIL(肿瘤浸润淋巴细胞)疗法——用于晚期黑色素瘤。此前,C-144-01研究(NCT02360579)的最新结果表明,TILs在标准ICI/靶向治疗失败的转移性黑色素瘤患者中具有疗效和安全性。
因此,该试验的结果以及近期FDA的批准,证明了利用细胞疗法填补晚期黑色素瘤患者治疗选择空白的可行性。本综述旨在通过阐述评估主要细胞疗法在黑色素瘤中疗效和安全性的最新多中心II/III期临床试验结果,全面概述已用于黑色素瘤的主要细胞疗法。
此外,我们总结了每种基于细胞的治疗选择目前的局限性,以及如何进一步推断这些基于细胞的疗法在晚期黑色素瘤中的未来方向。
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.
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