M.D. Anderson Cancer Center, University of Texas, Houston, TX 77054, USA.
J Immunother. 2013 May;36(4):276-86. doi: 10.1097/CJI.0b013e31829419f3.
Peptide vaccination against tumor-associated antigens remains one of the most common methods of immunization in cancer vaccine clinical trials. Although peptide vaccination has been reported to increase circulating antigen-specific T-cells, they have had limited clinical efficacy and there is a necessity to increase their capacity to generate strong antitumor responses. We sought to improve the clinical efficacy of peptide-based vaccines in cancer immunotherapy of metastatic melanoma using a LHRH agonist (leuprolide) as adjuvant. Seventy HLA-A0201 stage IIb-IV melanoma patients were vaccinated with class I HLA-A0201-restricted gp100209-2M peptide and stratified for HLA-DP4 restriction. HLA-DP4 patients were also vaccinated with class II HLA-DP4-restricted MAGE-3243-258 peptide. Patients from both groups were randomized to receive 2 doses of leuprolide or not. Here we report the increase in PBMC TREC levels at week 24 after peptide vaccination, which was independent of the leuprolide treatment. This change was mirrored by a small increase in the TREC-enriched CD8CD45RAROCD27CD103, but not the TREC-enriched CD4CD45RAROCD31 T-cell population. Serum concentration of 2 important factors for thymopoiesis was measured: insulin growth factor 1 (IGF-1) levels were not changed, whereas a moderate increase in IL-7 levels was noted in the sera of all patients 6 weeks after vaccination. Increased expression of CD127 (IL-7 receptor-α) at week 24, compared with baseline, was only seen in the CD8CD45RAROCD27CD103 T-cell population. Our results suggest that leuprolide has no effect on thymic output when used as peptide vaccine adjuvant, but IFA-based peptide vaccination may unexpectedly affect the thymus by increasing thymic output of new T cells.
肽疫苗接种针对肿瘤相关抗原仍然是癌症疫苗临床试验中最常见的免疫方法之一。尽管已经报道肽疫苗接种可以增加循环抗原特异性 T 细胞，但它们的临床疗效有限，因此有必要提高其产生强烈抗肿瘤反应的能力。我们试图使用 LHRH 激动剂（亮丙瑞林）作为佐剂来改善转移性黑色素瘤的基于肽的疫苗在癌症免疫治疗中的临床疗效。70 名 HLA-A0201 期 IIb-IV 期黑色素瘤患者接种了 I 类 HLA-A0201 限制性 gp100209-2M 肽，并按 HLA-DP4 限制进行分层。HLA-DP4 患者还接种了 II 类 HLA-DP4 限制性 MAGE-3243-258 肽。两组患者均随机接受 2 剂亮丙瑞林或不接受。在这里，我们报告了在肽疫苗接种后 24 周时 PBMC TREC 水平的增加，这与亮丙瑞林治疗无关。这种变化反映在 TREC 富集的 CD8CD45RAROCD27CD103 上略有增加，但 TREC 富集的 CD4CD45RAROCD31 T 细胞群没有增加。测量了对胸腺发生很重要的 2 个因素的血清浓度：胰岛素样生长因子 1（IGF-1）水平没有改变，而在接种疫苗后 6 周，所有患者的血清中均观察到 IL-7 水平中度增加。与基线相比，在第 24 周时，仅在 CD8CD45RAROCD27CD103 T 细胞群中观察到 CD127（IL-7 受体-α）的表达增加。我们的结果表明，亮丙瑞林作为肽疫苗佐剂使用时对胸腺输出没有影响，但基于 IFA 的肽疫苗接种可能会通过增加新 T 细胞的胸腺输出而意外地影响胸腺。
