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H-2不相容的淋巴因子激活的杀伤细胞(LAK细胞)的过继转移:一种利用小鼠模型成功进行癌症免疫治疗且无移植物抗宿主病(GVHD)的方法。

Adoptive transfer of H-2-incompatible lymphokine-activated killer (LAK) cells: an approach for successful cancer immunotherapy free from graft-versus-host disease (GVHD) using murine models.

作者信息

Toshitani A, Taniguchi K, Himeno K, Kawano Y, Nomoto K

机构信息

Department of Immunology, Kyushu University, Fukuoka, Japan.

出版信息

Cell Immunol. 1988 Sep;115(2):373-82. doi: 10.1016/0008-8749(88)90189-x.

Abstract

We investigated whether the adoptive transfer of H-2-incompatible lymphokine-activated killer (LAK) cells would efficiently demonstrate antitumor activity without damaging the normal host cells. Allogeneic LAK cells (5 X 10(7] did not cause graft-versus-host disease (GVHD) in irradiated recipients, whereas more than half of the mice transferred with the same dose of fresh allogeneic spleen cells developed GVHD. Repeated transfer (three times at 4-day intervals, 1.2 X 10(8) cells/mouse) did not result in GVHD. Graft-versus-host reaction (GVHR), which is detectable by spleen enlargement of recipients transferred with allogeneic lymphoid cells was also absent in LAK cell-transferred mice of all strain combinations tested. Host immune responses were not affected in these mice. Therefore, it is feasible to transfer allogeneic LAK cells. With the antitumor efficacy of allogeneic LAK cells, they preferentially lysed allogeneic tumor targets. Adoptive transfer of the allogeneic LAK cells led to a significant decrease in the lung-colonizing foci of intravenously inoculated B16 melanoma cells. Allogeneic LAK cells and syngeneic ones were equally active, in vivo. The use of allogeneic LAK cells may prove to be a valuable method for effective clinical antitumor immunotherapy.

摘要

我们研究了过继转移H-2不相容的淋巴因子激活的杀伤细胞(LAK细胞)是否能在不损伤正常宿主细胞的情况下有效发挥抗肿瘤活性。异基因LAK细胞(5×10⁷)在经照射的受体中未引发移植物抗宿主病(GVHD),而接受相同剂量新鲜异基因脾细胞转移的小鼠中超过半数发生了GVHD。重复转移(每隔4天转移一次,共三次,1.2×10⁸个细胞/只小鼠)未导致GVHD。在所有测试的品系组合中,接受LAK细胞转移的小鼠也未出现通过接受异基因淋巴细胞转移的受体脾脏肿大所检测到的移植物抗宿主反应(GVHR)。这些小鼠的宿主免疫反应未受影响。因此,转移异基因LAK细胞是可行的。鉴于异基因LAK细胞的抗肿瘤功效,它们优先裂解异基因肿瘤靶标。过继转移异基因LAK细胞导致静脉接种的B16黑色素瘤细胞在肺部的定植灶显著减少。在体内,异基因LAK细胞和同基因LAK细胞具有同等活性。使用异基因LAK细胞可能被证明是一种有效的临床抗肿瘤免疫治疗的有价值方法。

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