Minagawa H, Kakamu Y, Yoshida H, Tomita F, Oshima H, Mizuno D
Kato Memorial Bioscience Laboratories, Kyowa Hakko Kogyo Co., Ltd., Tokyo.
Jpn J Cancer Res. 1988 Mar;79(3):384-9. doi: 10.1111/j.1349-7006.1988.tb01602.x.
Induction of endogenous tumor necrosis factor (TNF) by administration of Bordetella pertussis vaccine (BPV) as a triggering agent and its therapeutic effect against MM46 carcinoma were investigated in C3H/He mice. Test triggering agents were injected intravenously into mice after intravenous injection of 4-fold dilution of macrophage activating factor (MAF) or 10(4) units of murine interferon-gamma (Mu-IFN-gamma). Then sera were obtained from the mice, and their TNF activities were assayed on L-929 cells by the method of Ruff and Gifford. The triggering activity of BPV was the highest among those of conventional triggers, such as lipopolysaccharide (LPS) of Escherichia coli, and OK-432. The levels of serum TNF activity triggered by BPV (4 X 10(9) cells), LPS of E. coli (3 micrograms) and OK-432 (3 KE) were 5350, 85 and 102 units/ml, respectively. Growth of MM46, a spontaneous mammary carcinoma cell line of C3H/He was observed for 35 days after tumor inoculation and was suppressed significantly by intravenous injection of MAF and BPV (4 X 10(9) cells). On local injection of BPV (2 X 10(9) cells) into murine tumors, complete regression was observed in 67% of the mice tested with or without MAF priming on day 25 after tumor inoculation, and intratumoral TNF activity was observed even in the case of the single injection of BPV.
在C3H/He小鼠中，研究了通过给予百日咳博德特氏菌疫苗（BPV）作为触发剂诱导内源性肿瘤坏死因子（TNF）及其对MM46癌的治疗效果。在静脉注射4倍稀释的巨噬细胞活化因子（MAF）或10⁴单位的小鼠干扰素-γ（Mu-IFN-γ）后，将测试触发剂静脉注射到小鼠体内。然后从小鼠中获取血清，并通过Ruff和Gifford的方法在L-929细胞上测定其TNF活性。在传统触发剂中，如大肠杆菌的脂多糖（LPS）和OK-432中，BPV的触发活性最高。由BPV（4×10⁹个细胞）、大肠杆菌LPS（3微克）和OK-432（3KE）触发的血清TNF活性水平分别为5350、85和102单位/毫升。在肿瘤接种后观察C3H/He自发乳腺癌细胞系MM46的生长35天，静脉注射MAF和BPV（4×10⁹个细胞）可显著抑制其生长。在小鼠肿瘤局部注射BPV（2×10⁹个细胞）后，在肿瘤接种后第25天，无论是否进行MAF预处理，67%的测试小鼠中观察到肿瘤完全消退，即使在单次注射BPV的情况下也观察到肿瘤内TNF活性。
