Ultimovacs ASA, Oslo, Norway.
Curr Opin Oncol. 2023 Mar 1;35(2):100-106. doi: 10.1097/CCO.0000000000000922. Epub 2023 Jan 16.
Checkpoint inhibitors (CPIs) have revolutionized treatment outcomes for patients with malignant melanoma. Long-term follow-up shows that a substantial subset of patients who exhibit clinical responses achieve extended overall survival. Nevertheless, most patients do not achieve durable benefit from CPIs, and improvements are urgently needed. The clinical efficacy of CPIs depends on highly variable preexisting spontaneous T-cell immune responses. Cancer vaccines represent an independent treatment modality uniquely capable of expanding the repertoire of tumor-specific T cells in cancer patients and thus have the capacity to compensate for the variability in spontaneous T-cell responses. Vaccines are, therefore, considered attractive components in a CPI-combination strategy.
Here we discuss recent results obtained through therapeutic vaccination against telomerase human telomerase reverse transcriptase (hTERT). Recent publications on translational research and clinical results from phase I trials indicate that vaccination against telomerase in combination with CPIs provides relevant immune responses, negligible added toxicity, and signals of clinical efficacy.
In the near future, randomized data from clinical trials involving therapeutic cancer vaccines and checkpoint inhibitors will be available. Positive readout may spark broad development and allow cancer vaccines to find their place in the clinic as an important component in multiple future CPI combinations.
检查点抑制剂 (CPIs) 彻底改变了恶性黑色素瘤患者的治疗效果。长期随访表明,相当一部分表现出临床反应的患者获得了延长的总生存期。然而,大多数患者并未从 CPIs 中获得持久获益,因此迫切需要进行改进。CPIs 的临床疗效取决于高度可变的预先存在的自发性 T 细胞免疫反应。癌症疫苗是一种独特的独立治疗方式,能够在癌症患者中扩增肿瘤特异性 T 细胞库,从而有能力弥补自发性 T 细胞反应的变异性。因此,疫苗被认为是 CPI 联合策略中具有吸引力的组成部分。
在这里,我们讨论了通过针对端粒酶人端粒酶逆转录酶 (hTERT) 的治疗性疫苗获得的最新结果。关于转化研究和 I 期临床试验的临床结果的最新出版物表明,端粒酶疫苗与 CPIs 的联合应用可提供相关的免疫反应、可忽略的附加毒性,并显示出临床疗效的信号。
在不久的将来,将有涉及治疗性癌症疫苗和检查点抑制剂的临床试验的随机数据。积极的研究结果可能会引发广泛的发展,并使癌症疫苗在临床上找到自己的位置,成为未来多种 CPI 联合方案的重要组成部分。