Kawakita M, Yoshida O, Ratliff T L
Department of Urology, Faculty of Medicine, Kyoto University.
Hinyokika Kiyo. 1997 Nov;43(11):835-8.
A promising approach to cancer immunotherapy is immunization with modified tumor cells carrying cytokine or immunomodulatory genes. Cytokine genes (tumor necrosis factor-alpha, interleukin 2, interferon gamma) and costimulatory molecule, B7-1, were incorporated into canarypox virus, ALVAC, which does not replicate in infected mammalian cells, and highly attenuated vaccinia virus, NYVAC. We examined the effect of local cytokine production on the growth of the mouse prostate tumor, RM-1, and the mouse bladder tumor, MBT-2. The vectors expressed the high levels of cytokines and B7-1 and the tumor growth of infected cells was significantly inhibited. The mice immunized with irradiated MBT-2 cells infected with ALVAC-interleukin 2 were protected against the subsequent challenge of parental tumor cells. We conclude that poxvirus vectors are useful for gene delivery in immunotherapy studies because of their infection efficiency, their capability of high gene product expression, their safety, and their case of handling.
一种很有前景的癌症免疫疗法是用携带细胞因子或免疫调节基因的修饰肿瘤细胞进行免疫接种。细胞因子基因(肿瘤坏死因子-α、白细胞介素2、干扰素γ)和共刺激分子B7-1被整合到金丝雀痘病毒ALVAC(其在受感染的哺乳动物细胞中不复制)和高度减毒的痘苗病毒NYVAC中。我们研究了局部细胞因子产生对小鼠前列腺肿瘤RM-1和小鼠膀胱肿瘤MBT-2生长的影响。这些载体表达高水平的细胞因子和B7-1,并且感染细胞的肿瘤生长受到显著抑制。用感染了ALVAC-白细胞介素2的经辐照的MBT-2细胞免疫的小鼠对随后亲本肿瘤细胞的攻击具有抵抗力。我们得出结论,痘病毒载体因其感染效率、高基因产物表达能力、安全性以及易于操作,在免疫疗法研究中可用于基因传递。