Induction of cytotoxic T lymphocytes from peripheral blood of human histocompatibility antigen (HLA)-A31(+) gastric cancer patients by in vitro stimulation with antigenic peptide of signet ring cell carcinoma.

Induction of cytotoxic T lymphocytes from peripheral blood of human histocompatibility antigen (HLA)-A31(+) gastric cancer patients by in vitro stimulation with antigenic peptide of signet ring cell carcinoma.
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DOI:
10.1111/j.1349-7006.2000.tb00990.x
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发表时间:
2000-06
期刊:
Japanese journal of cancer research : Gann
影响因子:
--
通讯作者:
Sato N
Sato N
中科院分区:
其他
文献类型:
--
作者:
Nabeta Y;Sahara H;Suzuki K;Kondo H;Nagata M;Hirohashi Y;Sato Y;Wada Y;Sato T;Wada T;Yamashita T;Kikuchi K;Sato N

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抗原肽已被用作黑色素瘤患者的癌症疫苗,并导致转移性肿瘤的急剧消退。然而,在非黑色素瘤肿瘤中发现的抗原很少。我们最近通过生化洗脱从人胃印细胞癌细胞系中纯化了一种新的天然抗原肽,命名为F4.2,并表明它被一个自体人组织相容性抗原(HLA) - A31 -限制性细胞毒性T淋巴细胞(CTL)克隆识别。在这里,我们描述了从HLA - A31+胃癌患者的外周血T淋巴细胞体外诱导F4.2‐特异性ctl。7例HLA - A31+胃癌患者的T细胞在体外被F4.2脉冲的自体树突状细胞刺激,这些树突状细胞是在粒细胞巨噬细胞集落刺激因子(GM - CSF)和IL - 4存在下培养的。在F4.2脉冲树突状细胞刺激3次后,我们通过6小时51Cr释放试验测试了T细胞对装载F4.2的C1R - A *31012的细胞毒性。在7名HLA - A31+患者中的2名患者的受刺激T细胞中检测到F4.2特异性细胞毒性。此外,两种F4.2‐特异性的ctl也裂解了胃癌细胞系HST‐2,F4.2来源于该细胞系。这些结果提示F4.2肽可能在某些胃癌患者中作为HLA - A31限制性肽疫苗有用。
Antigenic peptides have been used as a cancer vaccine in melanoma patients and have led to a drastic regression of metastatic tumors. However, few antigens have been identified in non‐melanoma tumors. We recently purified a new natural antigenic peptide, designated F4.2, by biochemical elution from a human gastric signet cell carcinoma cell line and showed that it is recognized by an autologous human histocompatibility antigen (HLA)‐A31‐restricted cytotoxic T lymphocyte (CTL) clone. Here we describe in vitro induction of F4.2‐specific CTLs from peripheral blood T lymphocytes of HLA‐A31+ gastric cancer patients. The T cells of seven HLA‐A31+ patients with gastric cancers were stimulated in vitro by F4.2‐pulsed autologous dendritic cells which had been induced from peripheral blood of each patient by incubation in the presence of granulocyte macrophage colony‐stimulating factor (GM‐CSF) and IL‐4. We tested the cytotoxicity of the T cells against F4.2‐loaded C1R‐A *31012 by a 6‐h 51Cr release assay after 3 stimulations with F4.2‐pulsed dendritic cells. F4.2‐specific cytotoxicity was detectable in the stimulated T cells from two of the seven HLA‐A31+ patients. Further, both F4.2‐specific CTLs also lysed the gastric cancer cell line, HST‐2, from which F4.2 was derived. These results suggest that F4.2 peptide may be useful as an HLA‐A31‐restricted peptide vaccine in certain patients with gastric cancer.
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