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コバヤシ ヒロヒト
KOBAYASHI Hirohito
小林 博人 所属 医学部 医学科（附属足立医療センター） 職種 准教授 |
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| 論文種別 | 原著 |
| 言語種別 | 英語 |
| 査読の有無 | 査読あり |
| 表題 | Synthesis of pyrophosphate-containing compounds that stimulate Vgamma2Vdelta2 T cells: application to cancer immunotherapy. |
| 掲載誌名 | 正式名：Medicinal chemistry (Shariqah (United Arab Emirates)) 略 称：Med Chem ISSNコード：15734064/15734064 |
| 掲載区分 | 国外 |
| 巻・号・頁 | 3(1),pp.85-99 |
| 著者・共著者 | Tanaka Y, Kobayashi H, Terasaki T, Toma H, Aruga A, Uchiyama T, Mizutani K, Mikami B, Morita C T, Minato N |
| 担当区分 | 2nd著者 |
| 発行年月 | 2007/01 |
| 概要 | Human Vgamma2Vdelta2 T cells recognize nonpeptide antigens, such as isoprenoid pyrophosphomonoester intermediates, alkylamine compounds, and bisphosphonate drugs, as well as some tumor cells. Although attempts have been made to derive novel cancer immunotherapies based on the discovery of these unconventional antigens, effective therapies remain to be developed. Here, we synthesized a series of pyrophosphate-containing compounds and examined the chemical requirements for the recognition of pyrophosphomonoester antigens by gammadelta T cells. The structural analysis clearly demonstrated that a proximal methylene moiety plays a crucial role in the stimulatory activity of the antigens. For optimal gammadelta T cell proliferation, we find that the use of human serum albumin was preferred and that pyrophosphomonoesters were superior to nitrogen-containing bisphosphonate compounds. Using these techniques, we have successfully expanded gammadelta T cells from healthy donors as well as from cancer patients using one of the most active compounds, 2-methyl-3-butenyl-1-pyrophosphate (2M3B1PP). The resulting expanded gammadelta T cells exhibited potent, cytotoxic activity against a wide variety of tumor cell lines. Even gammadelta T cells from a patient with advanced liver carcinoma efficiently responded to 2M3B1PP and exhibited strong cytotoxic activity against tumor cells. The pretreatment of tumor cells with nonpeptide antigens was essential for efficient cytotoxicity via TCR-gammadelta. The present study suggests a novel strategy for cancer immunotherapy using synthetic small pyrophosphate-containing compounds and nitrogen-containing bisphosphonates. |
| DOI | 10.2174/157340607779317544 |
| PMID | 17266628 |