Tang Yucheng, Akbulut Hakan, Maynard Jonathan, Petersen Line, Fang Xiangming, Zhang Wei-Wei, Xia Xiaoqin, Koziol James, Linton Phyllis-Jean, Deisseroth Albert
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
J Immunol. 2006 Oct 15;177(8):5697-707. doi: 10.4049/jimmunol.177.8.5697.
We showed that the Ad-sig-TAA/ecdCD40L vaccine induces a tumor suppressive immune response to the hMUC-1 and rH2N tumor-associated self Ags (TAA) and to the Annexin A1 tumor vascular Ag, even in mice in which anergy exists to these Ags. When the TAA/ecdCD40L protein is given s.c. as a boost following the Ad-sig-TAA/ecdCD40L vector, the levels of the TAA-specific CD8 T cells and Abs increase dramatically over that seen with vector alone, in young (2-mo-old) as well as old (18-mo-old) mice. The Abs induced against hMUC-1 react with human breast cancer. This vaccine also induces a 4-fold decrement of negative regulatory CD4CD25FOXP3-T cells in the tumor tissue of 18-mo-old mice. These results suggest that the Ad-sig-TAA/ecdCD40L vector prime-TAA/ecdCD40L protein boost vaccine platform may be valuable in reducing postsurgery recurrence in a variety of epithelial neoplasms.
我们发现，Ad-sig-TAA/ecdCD40L疫苗即使在对这些抗原存在无反应性的小鼠中，也能诱导针对人MUC-1和rH2N肿瘤相关自身抗原（TAA）以及膜联蛋白A1肿瘤血管抗原的肿瘤抑制性免疫反应。当在Ad-sig-TAA/ecdCD40L载体接种后，皮下给予TAA/ecdCD40L蛋白进行加强免疫时，在年轻（2月龄）和年老（18月龄）小鼠中，TAA特异性CD8 T细胞和抗体的水平比单独使用载体时显著增加。针对人MUC-1诱导产生的抗体可与人乳腺癌发生反应。该疫苗还能使18月龄小鼠肿瘤组织中负性调节性CD4CD25FOXP3+ T细胞数量减少4倍。这些结果表明，Ad-sig-TAA/ecdCD40L载体初免-TAA/ecdCD40L蛋白加强疫苗平台在降低多种上皮性肿瘤术后复发方面可能具有重要价值。
