Malignant melanoma has seen monumental changes in treatment options the last decade from the very poor results of dacarbazine treatment to the modern‐day use of targeted therapies and immune checkpoint inhibitors. Melanoma has a high mutational burden making it more capable of evoking immune responses than many other tumours. Even when considering double immune checkpoint blockade with anti‐CTLA‐4 and anti‐PD‐1, we still have far to go in melanoma treatment as 50% of patients with metastatic disease do not respond to current treatment. Alternative immunotherapy should therefore be considered. Since melanoma has a high mutational burden, it is considered more immunogenic than many other tumours. T cell receptor (TCR) therapy could be a possible way forward, either alone or in combination, to improve the response rates of this deadly disease. Melanoma is one of the cancers where TCR therapy has been frequently applied. However, the number of antigens targeted remains fairly limited, although advanced personalized therapies aim at also targeting private mutations. In this review, we look at possible aspects of targeting TCR therapy towards melanoma and provide an implication of its use in the future.

中文翻译：

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针对黑色素瘤的 T 细胞受体疗法 (TCR) - 未来的免疫疗法？


过去十年，恶性黑色素瘤的治疗选择发生了巨大变化，从达卡巴嗪治疗的效果非常差，到现代靶向治疗和免疫检查点抑制剂的使用。黑色素瘤具有较高的突变负担，使其比许多其他肿瘤更能引发免疫反应。即使考虑使用抗 CTLA-4 和抗 PD-1 双重免疫检查点阻断，我们在黑色素瘤治疗方面仍有很长的路要走，因为 50% 的转移性疾病患者对当前的治疗没有反应。因此，应考虑替代免疫疗法。由于黑色素瘤具有较高的突变负担，因此它被认为比许多其他肿瘤更具免疫原性。 T 细胞受体 (TCR) 疗法可能是一种可能的前进方向，无论是单独还是联合治疗，都可以提高这种致命疾病的反应率。黑色素瘤是TCR疗法经常应用的癌症之一。然而，尽管先进的个性化疗法也旨在针对私人突变，但针对的抗原数量仍然相当有限。在这篇综述中，我们研究了针对黑色素瘤的 TCR 靶向治疗的可能方面，并提供了其未来使用的启示。