Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5T4 (TroVax) is CD4+ T cell dependent and antibody mediated
Active treatment of murine tumors with a highly attenuated vaccinia virus expressing the tumor associated antigen 5T4 (TroVax) is CD4+ T cell dependent and antibody mediated
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DOI：
10.1007/s00262-005-0096-4
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发表时间：
2006-09-01
影响因子：
5.8
通讯作者：
Carroll, MW
中科院分区：
文献类型：
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作者：
Harrop, R;Ryan, MG;Carroll, MW
5T4 是一种肿瘤相关抗原，在多种人类腺癌表面表达。这种高度减毒的病毒，即安卡拉痘苗病毒，经过改造可表达人类 5T4 (h5T4)。在临床前小鼠模型中，重组病毒 (TroVax) 诱导保护免受 CT26-h5T4（表达 h5T4 的同基因肿瘤系）的攻击。抗肿瘤活性持续时间长，在最后一次疫苗接种后 6 个月仍具有明显的保护作用。在治疗环境中，给小鼠注射 TroVax 可使肿瘤负荷减少 > 90%。在主动治疗模型中，CD8+T细胞的耗竭对治疗没有影响，而CD4+T细胞的耗竭则完全消除抗肿瘤活性。在预防性环境中，诱导 h5T4 免疫反应后清除 CD4(+) 和 CD8(+) T 细胞对 CT26-h5T4 攻击后的保护没有有害影响。根据这些研究，研究了抗体在抵抗肿瘤攻击中的作用。 5T4 特异性多克隆血清可将肿瘤负荷降低约 70%。因此，我们得出结论，CD4(+) T 细胞对于诱导保护性免疫反应至关重要，并且抗体是该异种鼠肿瘤模型中可能的效应部分。
5T4 is a tumor associated antigen that is expressed on the surface of a wide spectrum of human adenocarcinomas. The highly attenuated virus, modified vaccinia Ankara, has been engineered to express human 5T4 (h5T4). In a pre-clinical murine model, the recombinant virus (TroVax) induces protection against challenge with CT26-h5T4 (a syngeneic tumor line expressing h5T4). Anti-tumor activity is long lived, with protection still evident 6 months after the final vaccination. In a therapeutic setting, injection of mice with TroVax results in a reduction in tumor burden of > 90%. Depletion of CD8(+) T cells has no effect upon therapy in the active treatment model, whereas depletion of CD4(+) T cells completely abrogates anti-tumor activity. In a prophylactic setting, depletion of CD4(+) and CD8(+) T cells after the induction of a h5T4 immune response has no deleterious effect on protection following challenge with CT26-h5T4. In light of these studies, the role of antibodies in protection against tumor challenge was investigated. 5T4 specific polyclonal serum decreased tumor burden by approximately 70%. Thus, we conclude that CD4(+) T cells are essential for the induction of a protective immune response and that antibodies are the likely effector moiety in this xenogeneic murine tumor model.