State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai 200433, PR of China.
J Immunother. 2010 Jun;33(5):453-60. doi: 10.1097/CJI.0b013e3181cf23a6.
Therapeutic vaccines of cancer are attractive for their capacity of breaking the immune tolerance and invoking long-term immune response targeting cancer cells without autoimmunity. An efficient antigen delivery system is the key issue of developing an effective cancer vaccine. Attenuated Salmonella typhimurium as the carrier of cancer vaccine are able to transfer DNA from the prokaryote to the eukaryote and preferentially replicate within the tumor tissue. Heat shock protein 70 delivers the tumor-associated antigens to antigen presenting cells through its polypeptide-binding domain and breaks immune tolerance of the cancer cells. Here we described a novel low-copy-number DNA vaccine based on the Hsp70-TAA complex and carried by the attenuated S. typhimurium strain SL3261. Oral administration of this vaccine elicited specific CTL-mediated lysis of the melanoma tumor cells and marked activation of the T-cells. The therapeutic vaccine effectively protected 57.1% C57BL/6J mice from lethal challenge with B16F10 melanoma tumor cells in prophylactic settings and eraicated 62.5% tumor growth in therapeutic settings. This approach may provide a new strategy for the prevention and treatment of cancer.
癌症治疗性疫苗具有打破免疫耐受并引发针对癌细胞的长期免疫反应而不产生自身免疫的能力，因此备受关注。有效的抗原递呈系统是开发有效癌症疫苗的关键问题。减毒鼠伤寒沙门氏菌作为癌症疫苗的载体能够将 DNA 从原核生物传递到真核生物，并在肿瘤组织内优先复制。热休克蛋白 70 通过其多肽结合域将肿瘤相关抗原递呈给抗原呈递细胞，从而打破癌细胞的免疫耐受。在这里，我们描述了一种基于 Hsp70-TAA 复合物的新型低拷贝数 DNA 疫苗，该疫苗由减毒鼠伤寒沙门氏菌 SL3261 株携带。口服该疫苗可引发针对黑色素瘤肿瘤细胞的特异性 CTL 介导的裂解，并显著激活 T 细胞。该治疗性疫苗在预防性治疗中有效保护 57.1%的 C57BL/6J 小鼠免受致命性 B16F10 黑色素瘤肿瘤细胞的攻击，并在治疗性治疗中消除了 62.5%的肿瘤生长。这种方法可能为癌症的预防和治疗提供一种新策略。
