Warren Patrick, Song Wendy, Holle Eric, Holmes Lilia, Wei Yangzhang, Li Jin, Wagner Thomas, Yu Xianzhong
Oncology Research Institute, Greenville Hospital System, SC 29605, USA.
Anticancer Res. 2002 Mar-Apr;22(2A):599-604.
Suicide gene therapy in combination with pro-drugs represents an attractive approach to the treatment of cancer. Unfortunately this approach is limited by difficulty in targeting all tumor cells, especially those at the distant metastases associated with the most complex tumors. For this reason, attempts to stimulate global anti-tumor immune responses at the sites of effective suicide gene/pro-drug-mediated tumor cell destruction are appealing. Here we show that, by including a gene coding for secreted secondary lymphoid tissue chemokine (SLC) along with the herpes simplex virus thymide kinase (HSV-TK) gene in a bicistronic vector for anti-tumor gene therapy in conjunction with the pro-drug ganciclovir (GCV), we are able to mediate a greatly enhanced anti-tumor effect in the murine B16 melanoma tumor model. The data presented suggests that this enhanced antitumor effect is the result of a strong induced CTL immune response resulting from the recruitment of immune cells to the site of HSV-TK/GCV-induced tumor destruction by the potent chemokine SLC.
自杀基因疗法与前体药物联合使用是一种颇具吸引力的癌症治疗方法。不幸的是，这种方法受到难以靶向所有肿瘤细胞的限制，尤其是那些与最复杂肿瘤相关的远处转移灶中的肿瘤细胞。因此，在有效的自杀基因/前体药物介导的肿瘤细胞破坏部位刺激全身性抗肿瘤免疫反应的尝试很有吸引力。在此我们表明，通过在用于抗肿瘤基因治疗的双顺反子载体中，将编码分泌型二级淋巴组织趋化因子（SLC）的基因与单纯疱疹病毒胸苷激酶（HSV-TK）基因一起，与前体药物更昔洛韦（GCV）联合使用，我们能够在小鼠B16黑色素瘤肿瘤模型中介导显著增强的抗肿瘤作用。所呈现的数据表明，这种增强的抗肿瘤作用是由强效趋化因子SLC将免疫细胞募集到HSV-TK/GCV诱导的肿瘤破坏部位，从而引发强烈的诱导性CTL免疫反应的结果。
