New strategy for the identification of squamous carcinoma antigens that induce therapeutic immune responses in tumor-bearing mice.
New strategy for the identification of squamous carcinoma antigens that induce therapeutic immune responses in tumor-bearing mice.
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鉴定在荷瘤小鼠中诱导治疗性免疫反应的鳞状癌抗原的新策略。
DOI：
10.1038/sj.cgt.7701023
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发表时间：
2007
影响因子：
6.4
通讯作者：
Cohen,EP
中科院分区：
文献类型：
--
作者：
O-Sullivan,I;Chopra,A;Kim,TS;Magnuson,S;Falduto,MT;Huang,J;Cohen,EP
本研究描述了一种新的策略，用于识别鳞状细胞癌抗原肿瘤相关抗原（TAA）。抗原是通过比较高度富集免疫细胞的鳞状细胞癌疫苗与非富集疫苗的微阵列发现的。通过将来自鳞状癌细胞系KLN 205细胞（DBA/2小鼠来源（H-2 d））的剪切的基因组DNA片段（25 kb）转移到LM成纤维细胞（C3 H/He来源，H-2 k）中来制备疫苗。转移的肿瘤DNA片段自发整合到受体细胞的基因组中，随着细胞分裂而复制并表达。由于预计只有一小部分转染细胞群包含包含指定TAA基因的DNA片段（绝大多数指定正常细胞成分），因此采用了一种新策略来富集TAA阳性细胞的疫苗。微阵列用于比较富集和非富集疫苗表达的基因。75个基因在来自富集疫苗的细胞中过表达。一种是细胞色素P450基因（家族2，亚家族e，多肽1）（Cyp 2 e1），在富集疫苗中过表达，但在非富集疫苗中未过表达。通过将Cyp 2 e1基因的357 bp片段转移到成纤维细胞系中制备鳞状细胞癌疫苗。在用该基因片段转染的细胞免疫的荷瘤小鼠中诱导了足以导致无限期存活的稳健免疫。
This study describes a new strategy for the identification of squamous carcinoma antigens tumor-associated antigens (TAA). The antigens were discovered by comparing microarrays of squamous carcinoma vaccines highly enriched for immunotherapeutic cells with non-enriched vaccines. The vaccines were prepared by transferring sheared genomic DNA fragments (25 kb) from KLN205 cells, a squamous carcinoma cell line (DBA/2 mouse origin (H-2 d) into LM fibroblasts (C3H/He origin, H-2 k). The transferred tumor DNA segments integrate spontaneously into the genome of the recipient cells, replicate as the cells divide and are expressed. As only a small proportion of the transfected cell population was expected to have incorporated DNA segments that included genes specifying TAA (the vast majority specify normal cellular constituents), a novel strategy was employed to enrich the vaccine for TAA-positive cells. Microarrays were used to compare genes expressed by enriched and non-enriched vaccines. Seventy-five genes were overexpressed in cells from the enriched vaccine. One, the gene for Cytochrome P450 (family 2, subfamily e, polypeptide 1)(Cyp2e1), was overexpressed in the enriched but not the non-enriched vaccine. A vaccine for squamous carcinoma was prepared by transfer of a 357 bp fragment of the gene for Cyp2e1 into the fibroblast cell line. Robust immunity, sufficient to result in indefinite survival, was induced in tumor-bearing mice immunized with cells transfected with this gene fragment.