Kikuchi T, Watanabe M, Ohno T
Department of Neurosurgery, Jikei University School of Medicine, Tokyo.
Jpn J Cancer Res. 1991 Mar;82(3):339-45. doi: 10.1111/j.1349-7006.1991.tb01851.x.
Tumor-infiltrating lymphocytes (TIL) were generated from 10 glioma specimens by using recombinant interleukin-2 and an anti-CD3 antibody (CD3 + TILs). We obtained more than 1 x 10(9) cells in 5 cases, more than 5 x 10(8) cells in 2 cases, and about 1 x 10(8) cells in 3 cases during three weeks of incubation from small specimens ranging in weight from 0.5 to 2.0 g. In 4 cases, TILs were expanded following stimulation with only rIL-2 (CD3-TILs). The growth rate of CD3-TILs was less than that of CD3 + TILs. Cytotoxicity of CD3 + TILs was lower than that of lymphokine-activated killer (LAK) cells in a standard 4h 51Cr release assay. Cold target inhibition was undertaken in three cases and specific cytotoxicity could be shown in only one case. CD3 + TILs mainly consisted of CD3-positive cells, ranging from 63.2 to 99.9%. The ratio of CD4-positive cells to CD8-positive cells was not constant. The expression of Leu 7 and CD16 was low. The present study did not confirm previous findings that TILs were more tumor-selective and potent than LAK cells. Furthermore, the results on in vitro antitumor activity of those cells were not necessarily consistent with the results on their clinical activity. Further careful work is necessary on the preparation of immunocytes and the subsequent adoptive immunotherapy.
通过使用重组白细胞介素-2和抗CD3抗体(CD3 + TILs),从10例胶质瘤标本中生成肿瘤浸润淋巴细胞(TIL)。在为期三周的培养过程中,我们从重量为0.5至2.0 g的小标本中,5例获得了超过1×10⁹个细胞,2例获得了超过5×10⁸个细胞,3例获得了约1×10⁸个细胞。在4例中,仅用重组白细胞介素-2刺激后TILs得以扩增(CD3 - TILs)。CD3 - TILs的生长速率低于CD3 + TILs。在标准的4小时⁵¹Cr释放试验中,CD3 + TILs的细胞毒性低于淋巴因子激活的杀伤细胞(LAK)。对3例进行了冷靶抑制试验,仅1例显示出特异性细胞毒性。CD3 + TILs主要由CD3阳性细胞组成,占比从63.2%至99.9%。CD4阳性细胞与CD8阳性细胞的比例并不恒定。Leu 7和CD16的表达较低。本研究未证实先前的发现,即TILs比LAK细胞更具肿瘤选择性且更有效。此外,这些细胞的体外抗肿瘤活性结果与其临床活性结果不一定一致。在免疫细胞的制备及随后的过继性免疫治疗方面,还需要进一步细致的工作。