Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1–Her2_(341–456) fusion protein  

作　　者：Qiang Fu Yanfeng Wu Fang Yan Ning Wang Wenying Wang Xuetao Cao Yajie Wang Tao Wan 

机构地区：[1]Department of Oncology,Changhai Hospital of Shanghai,Shanghai 200433,China [2]National Key Laboratory of Medical Immunology and Institute of Immunology,Second Military Medical University,Shanghai 200433,China

出　　处：《Cellular & Molecular Immunology》2011年第5期424-432,共9页中国免疫学杂志（英文版）

基　　金：supported by the Major Program of the Shanghai Committee of Science and Technology Development(QF,06DZ19010);the National High Technology Research and Development Program of China(YFW,2009AA02Z102);the National Natural Science Foundation of China(YFW,30872296);the National Science and Technology Major Project of the Ministry of Science and Technology of China(TWan,2008ZX09101-043).

摘　　要：Heat shock proteins(HSPs)have been shown to interact with antigen-presenting cells(APCs),especially dendritic cells(DCs).HSPs act as potent adjuvants,inducing a Th1 response,as well as antigen-specific CD8^(+) cytotoxic T lymphocytes(CTL)via cross-presentation.Our previous work has demonstrated that Hsp70-like protein 1(Hsp70L1),a new member of the Hsp70 subfamily,can act as a powerful Th1 adjuvant in a DC-based vaccine.Here we report the efficient induction of tumor antigen-specific T cell immune response by DCs pulsed with recombinant fusion protein of Hsp70L1 and Her2_(341–456),the latter of which is a fragment of Her2/neu(Her2)containing E75(a HLA-A2 restricted CTL epitope).The fusion protein Hsp70L1–Her2_(341–456) promotes the maturation of DCs and activates them to produce cytokines,such as IL-12 and TNF-a,and chemokines,such as MIP-1a,MIP-1b and RANTES.Taken together,these results indicate that the adjuvant activity of Hsp70L1 is maintained in the fusion protein.Her2-specific HLA-A2.1-restricted CD8^(+) CTLs can be generated efficiently either from the Peripheral blood lymphocytes(PBL)of healthy donors or from the splenocytes of immunized HLA-A2.1/K^(b) transgenic mice by in vitro stimulation or immunization with DCs pulsed with the Hsp70L1–Her2_(341–456) fusion protein.This results in more potent target cell killing in an antigen-specific and HLA-A2.1-restricted manner.Adoptive transfer of splenocytes from transgenic mice immunized with Hsp70L1–Her2_(341–456)-pulsed DCs can markedly inhibit tumor growth and prolong the survival of nude mice with Her2^(+)/HLA-A2.1^(+) human carcinomas.These results suggest that Hsp70L1–Her2_(341–456)-pulsed DCs could be a new therapeutic vaccine for patients with Her2^(+) cancer.

关 键 词：CTL dendritic cell heat shock protein HER2/NEU immunotherapy 

分 类 号：R73[医药卫生—肿瘤]