Sakamoto Shinjiro, Matsueda Satoko, Takamori Shinzo, Toh Uhi, Noguchi Masanori, Yutani Shigeru, Yamada Akira, Shichijo Shigeki, Yamada Teppei, Suekane Shigetaka, Kawano Kouichiro, Naitou Masayasu, Sasada Tetsuro, Hattori Noboru, Kohno Nobuoki, Itoh Kyogo
Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan.
Cancer Vaccine Center, Kurume University, Kurume, Japan.
Cancer Sci. 2017 Apr;108(4):598-603. doi: 10.1111/cas.13189. Epub 2017 Apr 21.
The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11 /A11 (n = 18) or -A33 /A33 (n = 13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon (n = 4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas (2 or 2), and so on. For PPV, a maximum of four peptides were selected from nine different peptides capable of binding to HLA-A11 and -A33 molecules based on the pre-existing peptide-specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide-specific CTL responses were augmented in 4/12 or 2/9 of HLA-A11 /A11 or -A33 /A33 patients, while peptide-specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of four stable diseases and 14 progressive diseases in HLA-A11 /A11 patients, versus seven and six in -A33 /A33 patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses.
HLA - A11或 - A33等位基因分别在约18%或10%的亚洲人群中被发现,但在全球范围内它们均为次要等位基因,因此此前未进行过临床试验。为针对它们各自研发一种治疗性肽疫苗,我们研究了HLA - A11 /A11(n = 18)或 - A33 /A33(n = 13)等位基因的晚期癌症患者对个性化肽疫苗(PPV)方案的免疫反应。HLA - A11 +/A11 +或 - A33 +/A33 +患者的主要发病部位为结肠(n = 4或2)、胃(2或3)、乳腺(3或2)、肺和胰腺(2或2)等。对于PPV,基于预先存在的肽特异性IgG反应,从九种能够与HLA - A11和 - A33分子结合的不同肽中最多选择四种肽。未发生与PPV相关的严重不良事件。在第一个周期结束时,HLA - A11 /A11或 - A33 /A33患者中分别有4/12或2/9的患者肽特异性CTL反应增强,而分别有6/14或4/10的患者肽特异性IgG反应增强。HLA - A11 /A11患者的临床反应包括4例病情稳定和14例病情进展,而 - A33 /A33患者分别为7例和6例。鉴于其安全性和积极的免疫反应,可推荐对PPV进行进一步的临床研究。