Immunological evaluation of peptide vaccination for cancer patients with the HLA-A26 allele.
Immunological evaluation of peptide vaccination for cancer patients with the HLA-A26 allele.
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DOI：
10.1111/cas.12757
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发表时间：
2015-10
期刊：
影响因子：
5.7
通讯作者：
Itoh K
中科院分区：
文献类型：
--
作者：
Sakamoto S;Matsueda S;Takamori S;Toh U;Noguchi M;Yutani S;Yamada A;Shichijo S;Yamada T;Suekane S;Kawano K;Sasada T;Hattori N;Kohno N;Itoh K
为了开发用于具有HLA-A26等位基因的癌症患者的肽疫苗，其在世界范围内是少数群体，我们研究了HLA-A26+/A26+癌症患者在个性化肽疫苗方案下对四种不同CTL表位肽的免疫应答。在个性化肽疫苗方案中，从适用于HLA-A26+/A26+癌症患者的四种肽候选物中选择在接种前血浆中显示阳性肽特异性IgG应答的两种至四种肽，并皮下施用。肽特异性CTL和IgG应答沿着细胞因子水平在疫苗接种之前和之后测量。还测量了PBMC中的细胞表面标志物和血浆细胞因子水平。在这项研究中，21名晚期癌症患者，包括7名肺癌，3名乳腺癌，2名胰腺癌和2名结肠癌患者，入选。HLA-A26基因型为HLA-A26：01（n = 24）、HLA-A26：03（n = 10）和HLA-A26：02（n = 8）。分别有1例、14例和6例患者接受了2种、3种和4种肽。在大多数患者中观察到注射部位的1级或2级皮肤反应，但未观察到与疫苗接种相关的严重不良事件。肽特异性CTL应答分别在39%或22%的患者中在一个或两个周期的疫苗接种后增强。值得注意的是，在一个或两个周期的疫苗接种后，肽特异性IgG分别在63%或100%的患者中增加。这四个CTL表位肽的个性化肽疫苗可能是可行的HLA-A26+晚期癌症患者，因为他们的安全性和较高的免疫应答率。
To develop a peptide vaccine for cancer patients with the HLA-A26 allele, which is a minor population worldwide, we investigated the immunological responses of HLA-A26+/A26+ cancer patients to four different CTL epitope peptides under personalized peptide vaccine regimens. In personalized peptide vaccine regimens, two to four peptides showing positive peptide-specific IgG responses in pre-vaccination plasma were selected from the four peptide candidates applicable for HLA-A26+/A26+ cancer patients and administered s.c. Peptide-specific CTL and IgG responses along with cytokine levels were measured before and after vaccination. Cell surface markers in PBMCs and plasma cytokine levels were also measured. In this study, 21 advanced cancer patients, including seven lung, three breast, two pancreas, and two colon cancer patients, were enrolled. Their HLA-A26 genotypes were HLA-A26:01 (n = 24), HLA-A26:03 (n = 10), and HLA-A26:02 (n = 8). One, 14, and 6 patients received two, three, and four peptides, respectively. Grade 1 or 2 skin reactions at the injection sites were observed in the majority of patients, but no severe adverse events related to the vaccination were observed. Peptide-specific CTL responses were augmented in 39% or 22% of patients after one or two cycles of vaccination, respectively. Notably, peptide-specific IgG were augmented in 63% or 100% of patients after one or two cycles of vaccination, respectively. Personalized peptide vaccines with these four CTL epitope peptides could be feasible for HLA-A26+ advanced cancer patients because of their safety and higher rates of immunological responses.