Akaza H, Iwasaki A, Ohtani M, Ikeda N, Niijima K, Toida I, Koiso K
Department of Urology, University of Tsukuba, Ibaraki, Japan.
Cancer. 1993 Jul 15;72(2):558-63. doi: 10.1002/1097-0142(19930715)72:2<558::aid-cncr2820720237>3.0.co;2-h.
Antitumor effects of Bacillus Calmette-Guérin (BCG) against superficial urinary bladder cancer is known to be strong when BCG is directly infused into the bladder cavity. For expression of that effect, attachment of BCG to tumor cells is reported to be essential as the first step. Our study was conducted to elucidate the significance of attachment of BCG to tumor cells in inducing the antitumor effect.
BCG, Tokyo 172 strain, in the form of live bacilli, lyophilized bacilli, or autoclaved bacilli was co-cultured with MBT-2, mouse-origin transitional cell cancer cells. Various preparations of BCG were mixed with MBT-2 cells and transplanted to male C3H/He mice to see tumor growth-inhibiting effect.
Both live and lyophilized BCG attached strongly to MBT-2 cells. The maximal attachment to the cells with live BCG occurred 24 hours earlier than with lyophilized BCG. When BCG was autoclaved, it lost the ability to attach to the cells. Lyophilized or autoclaved BCG exerted a marked tumor growth-inhibiting effects. This effect was equal to the Tokyo 172 strain and the Armand Frappier Canada strain. Histologically, a high degree of infiltration by macrophages was seen.
The results indicated that coexistence of BCG, even as killed by autoclaving, with tumor cells activates local immunity. Accordingly, the significance of the attachment of BCG to tumor cells in intravesical infusion therapy is surmised to lie in the fact that it results in retention of the BCG at the reaction site. This may provide a clue on how to approach future development of safer and more stable BCG-derived antitumor drugs.
已知卡介苗（BCG）直接注入膀胱腔时对浅表性膀胱癌具有很强的抗肿瘤作用。据报道，BCG附着于肿瘤细胞是发挥该作用的第一步，至关重要。我们开展本研究以阐明BCG附着于肿瘤细胞在诱导抗肿瘤作用中的意义。
将东京172株活芽孢杆菌、冻干芽孢杆菌或高压灭菌芽孢杆菌形式的BCG与小鼠来源的移行细胞癌细胞MBT-2共培养。将各种BCG制剂与MBT-2细胞混合后移植到雄性C3H/He小鼠体内，观察肿瘤生长抑制效果。
活BCG和冻干BCG均能强烈附着于MBT-2细胞。活BCG对细胞的最大附着时间比冻干BCG早24小时。当BCG经过高压灭菌后，它失去了附着于细胞的能力。冻干或高压灭菌的BCG均具有显著的肿瘤生长抑制作用。该作用与东京172株及加拿大阿尔芒·弗拉皮耶株相当。组织学检查可见巨噬细胞高度浸润。
结果表明，即使经高压灭菌杀死的BCG与肿瘤细胞共存也能激活局部免疫。因此，推测BCG在膀胱内灌注治疗中附着于肿瘤细胞的意义在于它能使BCG保留在反应部位。这可能为未来开发更安全、更稳定的BCG衍生抗肿瘤药物提供思路。
