Goto S, Suma Y, Noguchi K, Kera J, Sakai S, Soma G I, Takeuchi S
Biotechnology Research Center, Teikyo University, Kanagawa, Japan.
Cancer Biother. 1995 Spring;10(1):37-44. doi: 10.1089/cbr.1995.10.37.
The effect of TNF-SAM2 on cytotoxic activity of tumor-infiltrating lymphocytes (TIL) was investigated. TIL were prepared from 11 human cancer patients. They were propagated by double in vitro stimulation with anti-CD3 monoclonal antibody and interleukin-2, and cultured for 3 weeks. The cytotoxic activity of TIL was tested with standard 4h 51Cr-release assays in the presence or the absence of TNF-SAM2. In the presence of TNF-SAM2 (500U/ml), the mean cytotoxic activity against autologous tumor cells was significantly augmented compared to that in its absence. However, the fact that cytotoxic activity against K562 and Daudi showed no difference whether substance was present or not, indicates that LAK and NK activity were not affected by TNF-SAM2. Direct cytotoxicity by exogenously added TNF-SAM2 to tumor cells was measured in 9 out of 11 cases and this revealed that cytotoxicity solely by TNF-SAM2 was seen in 3 tumors. However, there was no correlation between the augmentation of cytotoxicity by TIL in the presence of TNF-SAM2 and the cytotoxicity shown by TNF-SAM2 alone. These results suggested that TIL therapy combined with administration of exogenous TNF may exert a synergistically stronger therapeutic effect on cancer.
研究了TNF-SAM2对肿瘤浸润淋巴细胞(TIL)细胞毒性活性的影响。TIL取自11例人类癌症患者。通过用抗CD3单克隆抗体和白细胞介素-2进行双重体外刺激使其增殖,并培养3周。在有或无TNF-SAM2的情况下,用标准的4小时51Cr释放试验检测TIL的细胞毒性活性。在存在TNF-SAM2(500U/ml)的情况下,与不存在时相比,对自体肿瘤细胞的平均细胞毒性活性显著增强。然而,对K562和Daudi的细胞毒性活性在有无该物质时均无差异这一事实表明,LAK和NK活性不受TNF-SAM2影响。在11例中的9例中检测了外源添加的TNF-SAM2对肿瘤细胞的直接细胞毒性,结果显示仅在3种肿瘤中观察到TNF-SAM2单独的细胞毒性。然而,在存在TNF-SAM2的情况下TIL细胞毒性的增强与TNF-SAM2单独显示的细胞毒性之间没有相关性。这些结果表明,TIL疗法联合外源性TNF给药可能对癌症产生协同更强的治疗效果。