单细胞追踪揭示黑色素瘤 TIL 治疗过程中肿瘤反应性 T 细胞的可塑性
Single-cell tracking reveals tumor-reactive T cell plasticity during melanoma TIL therapy.
TIL(肿瘤浸润淋巴细胞)过继细胞治疗可在转移性黑色素瘤中诱导持久缓解,然而在体外扩增过程中及回输后,调控肿瘤反应性T细胞命运的克隆和转录动态仍知之甚少。
英文原题:Adoptive Cell Transfer and Vaccines in Melanoma: The Horizon Comes Into View.
在过去四十年中,针对黑色素瘤的癌症免疫治疗已从单药I型细胞因子治疗发展到联合免疫检查点抑制。
在过去四十年中,黑色素瘤的癌症免疫治疗已从单药I型细胞因子治疗演变为联合免疫检查点抑制。在此过程中,细胞治疗和癌症疫苗领域也取得了突破。早期过继性细胞治疗的数据——涉及输注从切除肿瘤中采集的TIL(肿瘤浸润淋巴细胞)——是在美国国家癌症研究所产生的。随后,全球有限数量的中心建立了提供这些疗法的项目。近年来,通过集中进行TIL(肿瘤浸润淋巴细胞)产品的生长和扩增,然后将产品分发至众多学术医疗中心以实施治疗,该疗法的可及性已变得更加广泛。目前正在开展工作,以利用额外的细胞类型和/或修饰的细胞产品来优化这些治疗,并确定将这些治疗与免疫检查点抑制相结合的最佳方式。同样,肿瘤疫苗策略正在经历剧烈变革,该领域正从基于肽的疫苗转向下一代测序和T细胞受体测序。这些变化通过寻找更具免疫原性的选择,有助于改进靶抗原的选择,并有助于脂质纳米颗粒和mRNA递送的发展。简而言之,正在彻底改变传染病疫苗接种的方法的演变一直在持续,并且在黑色素瘤患者中已有有希望的初步数据。
Over the past four decades, cancer immunotherapy for melanoma has evolved from single-agent, type-I cytokine therapy to combination immune checkpoint inhibition. Along the way, breakthroughs in the fields of cell therapy and cancer vaccination have been made as well. The early data from adoptive cell therapy, involving the delivery of tumor infiltrating lymphocytes harvested from resected tumors, was generated at the National Cancer Institute. Subsequently, a limited number of centers across the globe have developed programs to deliver these therapies. Recently, more widespread availability of this therapy has been made possible by centralizing the growth and expansion of tumor infiltrating lymphocyte products, then distributing the products for delivery of therapy at numerous academic medical centers. Work is ongoing to optimize these treatments with additional cell types and/or modified cell products, and to determine the best ways of combining these treatments with immune checkpoint inhibition. Similarly, tumor vaccination strategies are undergoing dramatic changes, transitioning the field from peptide-based vaccines to next-generation sequencing and T-cell receptor sequencing. These changes help improve the selection of targeted antigens by finding more immunogenic options, and they help with the development of lipid nanoparticles and mRNA delivery. In short, evolution of the approaches that are revolutionizing infectious disease vaccination has been ongoing, and there are promising preliminary data in patients with melanoma.
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