A Mage3/Heat Shock Protein70 DNA vaccine induces both innate and adaptive immune responses for the antitumor activity
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- 作者：Lifeng Wang ; Lisa Rollins ; Qinlong Gu ; Si-Yi Chen ; Xue F. Huang
- 关键词：DNA vaccine ; Mage3 ; Heat shock protein ; Antitumor activity
- 刊名：Vaccine
- 出版年：2009
- 出版时间：11 December 2009
- 年：2009
- 卷：28
- 期：2
- 页码：561-570
- 全文大小：1210 K
文摘
Heat shock proteins (HSPs) are highly effective and versatile molecules in promoting antitumor immune responses. We tested whether a HSP-based DNA vaccine can induce effective immune response against Mage3, a cancer testis (CT) antigen frequently expressed in many human tumors, thereby controlling the Mage3-expressing tumor. The vaccine was constructed by linking human inducible HSP70 to the C-terminus of a modified Mage3 gene (sMage3) that was attached at its N-terminus with the signal leader sequence of the human RANTES for releasing the expressed fusion protein from the transduced cells. Intramuscular injection of sMage3Hsp DNA induced CD4+/CD8+ T cell and antibody responses. Vaccination with sMage3Hsp DNA was more effective in inhibiting Mage3-expressing TC-1 tumors. When we dissected the antitumor activity of CD4+ and CD8+ T cells by immunizing CD4+ and CD8+ knockout mice with sMage3Hsp DNA, we found that both CD8+ T and CD4+ T cells played a role in control of inoculated tumor, but did not constitute the whole of immune protection in the prophylactic immunization. Instead, depletion of natural killer (NK) cells led to a major loss of antitumor activity in the immunized mice. These results indicate that the HSP-based Mage3 DNA vaccine can more effectively inhibit tumor growth by inducing both the innate immune responses and Mage3-specific adaptive immune responses via the Hsp-associated adjuvant function.