Dillman Robert O, Nistor Gabriel I, Cornforth Andrew N
AiVita Biomedical, Inc., 18301 Von Karman Avenue, Suite 130, Clinical, Research, and Manufacturing Departments, Irvine, CA 92612, USA.
Melanoma Manag. 2016 Dec;3(4):273-289. doi: 10.2217/mmt-2016-0014. Epub 2016 Nov 29.
Administering dendritic cells (DC) loaded with tumor-associated antigens (TAA) is a promising strategy for therapeutic vaccines in advanced melanoma. To date the induction of immune responses to specific TAA has been more impressive than clinical benefit because of TAA limitations, suboptimal DC and possibly immune-checkpoint inhibition. Various products, antigen-loading techniques, treatment schedules, routes of administration and adjunctive agents continue to be explored. Biologic heterogeneity suggests autologous tumor as the optimal TAA source to induce immune responses to the entire repertoire of unique patient-specific neoantigens. Many questions remain regarding the optimal preparation of DC and strategies for antigen loading. Effective DC vaccines should result in additive or synergistic effects when combined with checkpoint inhibitors.
给予负载肿瘤相关抗原(TAA)的树突状细胞(DC)是晚期黑色素瘤治疗性疫苗的一种有前景的策略。迄今为止,由于TAA的局限性、DC不够理想以及可能存在的免疫检查点抑制,针对特定TAA的免疫反应诱导在临床上比实际获益更令人印象深刻。各种产品、抗原负载技术、治疗方案、给药途径和辅助剂仍在不断探索中。生物异质性表明自体肿瘤是诱导针对患者特异性独特新抗原全部组成的免疫反应的最佳TAA来源。关于DC的最佳制备和抗原负载策略仍存在许多问题。有效的DC疫苗与检查点抑制剂联合使用时应产生相加或协同效应。