Guilhem Richard, Nicole Ruggiero, Gary D Steinberg, William D Martin, Anne S De Groot
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引用次数: 0
Abstract
Introduction: Clinical trials of personalized cancer vaccines have shown that on-demand therapies that are manufactured for each patient, result in activated T cell responses against individual tumor neoantigens. However, their use has been traditionally restricted to adjuvant settings and late-stage cancer therapy. There is growing support for the implementation of PCV earlier in the cancer therapy timeline, for reasons that will be discussed in this review.
Areas covered: The efficacy of cancer vaccines may be to some extent dependent on treatment(s) given prior to vaccine administration. Tumors can undergo radical immunoediting following treatment with immunotherapies, such as checkpoint inhibitors, which may affect the presence of the very mutations targeted by cancer vaccines. This review will cover the topics of neoantigen cancer vaccines, tumor immunoediting, and therapy timing.
Expert opinion: Therapy timing remains a critical topic to address in optimizing the efficacy of personalized cancer vaccines. Most personalized cancer vaccines are being evaluated in late-stage cancer patients and after treatment with checkpoint inhibitors, but they may offer a greater benefit to the patient if administered in earlier clinical settings, such as the neoadjuvant setting, where patients are not facing T cell exhaustion and/or a further compromised immune system.
导言:个性化癌症疫苗的临床试验表明,为每位患者按需制造的疗法可产生针对单个肿瘤新抗原的活化 T 细胞反应。然而,这些疫苗的使用传统上仅限于辅助治疗和晚期癌症治疗。越来越多的人支持在癌症治疗的早期阶段使用 PCV,原因将在本综述中讨论:癌症疫苗的疗效在一定程度上取决于接种疫苗前的治疗。在接受免疫疗法(如检查点抑制剂)治疗后,肿瘤可能会发生彻底的免疫编辑,这可能会影响癌症疫苗所针对的突变的存在。本综述将涵盖新抗原癌症疫苗、肿瘤免疫编辑和治疗时机等主题:治疗时机仍是优化个性化癌症疫苗疗效的关键问题。大多数个性化癌症疫苗都是在晚期癌症患者和接受检查点抑制剂治疗后进行评估的,但如果在较早的临床环境中(如新辅助治疗环境)给药,患者可能会获得更大的益处,因为在新辅助治疗环境中,患者不会面临T细胞衰竭和/或免疫系统进一步受损的情况。
期刊介绍:
Expert Review of Vaccines (ISSN 1476-0584) provides expert commentary on the development, application, and clinical effectiveness of new vaccines. Coverage includes vaccine technology, vaccine adjuvants, prophylactic vaccines, therapeutic vaccines, AIDS vaccines and vaccines for defence against bioterrorism. All articles are subject to rigorous peer-review.
The vaccine field has been transformed by recent technological advances, but there remain many challenges in the delivery of cost-effective, safe vaccines. Expert Review of Vaccines facilitates decision making to drive forward this exciting field.