悪性黒色腫に対する樹状細胞(Dendritic cells)を用いた免疫療法  [in Japanese] Vaccination of Malignant Melanoma Patients with Autologous Tumor-Lysate Pulsed Dendritic Cells  [in Japanese]

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Author(s)

Abstract

遠隔転移を有し,標準的な前治療が無効であった悪性黒色腫患者3例を対象として樹状細胞ワクチンによる免疫療法を試みた.Nestleらの方法に従い,末梢血単球から樹状細胞を誘導し,自己の腫瘍融解液で刺激後さらに成熟させた樹状細胞を一定の間隔でリンパ節内に投与した.重篤な副作用はみられなかったが,全例において治療中に転移巣の増大と新生がみられたため,本治療は無効と判定された.ただし,2例で治療開始後白斑が出現し,そのうち1例では一部の転移巣の縮小が観察された.縮小した転移巣の生検標本ではTIA-1陽性memory T細胞の浸潤が多くみられた.さらに,2例において治療開始6~14週後に腫瘍融解液で刺激した樹状細胞に対する遅延型皮膚反応が誘発された.以上の所見から,特異的免疫反応の誘導が示唆された.しかし,原発および転移腫瘍の免疫組織化学的検索では,全例において転移巣のHLA class1分子の発現が消失もしくは減弱しており,それが本治療が無効であった理由のひとつと考えられた.

We report a phase I trial in melanoma patients using tumor-lysates pulsed dentritic cells (DCs). DCs were generated from peripheral blood in the presence of granulocyte/macrophage-colony stimulating factor and inrterleukin 4 and were pulsed with autologous tumor lysates. Three patients with advanced melanoma received 5~8 intra-lymph-node infusions of DCs. Although regression of individual skin metastasis was evident in one patient, increased size of metastases and/or development of new lesions were observed in all three patients during the therapy. Clinical side effects were mild. Two patients developed vitiligo after DC vaccinations. DTH reactivity toward tumor lysates was induced in two patients. Resolution of skin metastases and positive DTH response site were accompanied CD8+/CD45RO+ lymphocytic infiltration. Immunohistochemical study revealed down-regulation of HLA class I antigen and β2 microglobulin in both primary and metastatic lesions of these three patients. These results suggested that HLA-class 1 down-regulation plays a role in immune escape from cytotoxic T cells.

Journal

  • The Japanese Journal of Dermatology

    The Japanese Journal of Dermatology 112(1), 9-16, 2002-01-20

    Japanese Dermatological Association

References:  20

Cited by:  2

Codes

  • NII Article ID (NAID)
    10008386383
  • NII NACSIS-CAT ID (NCID)
    AN00196602
  • Text Lang
    JPN
  • Article Type
    Journal Article
  • ISSN
    0021499X
  • NDL Article ID
    025117239
  • NDL Call No.
    Z19-202
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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