Oncotarget

Research Papers:

The novel complex combination of alum, CpG ODN and HH2 as adjuvant in cancer vaccine effectively suppresses tumor growth in vivo

Yaomei Tian, Meng Li, Chaoheng Yu, Rui Zhang, Xueyan Zhang, Rong Huang, Lian Lu, Fengjiao Yuan, Yingzi Fan, Bailing Zhou, Ke Men, Heng Xu and Li Yang _

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Oncotarget. 2017; 8:45951-45964. https://doi.org/10.18632/oncotarget.17504

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Abstract

Yaomei Tian1,*, Meng Li2,*, Chaoheng Yu1, Rui Zhang1, Xueyan Zhang1, Rong Huang1, Lian Lu1, Fengjiao Yuan1, Yingzi Fan1, Bailing Zhou1, Ke Men1, Heng Xu1 and Li Yang1

1State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China

2Chengdu Blood Center, Chengdu, Sichuan, China

*These authors contributed equally to this work

Correspondence to:

Li Yang, email: [email protected]

Keywords: combinatorial adjuvant, aluminum salts, CpG oligodeoxynucleotide, innate defense regulator peptide HH2, anti-tumor immune responses

Received: December 07, 2016    Accepted: April 02, 2017    Published: April 28, 2017

ABSTRACT

Single-component adjuvant is prone to eliciting a specific type of Th1 or Th2 response. So, the development of combinatorial adjuvants inducing a robust mixed Th1/Th2 response is a promising vaccination strategy against cancer. Here, we describe a novel combination of aluminum salts (alum), CpG oligodeoxynucleotide (CpG) and innate defense regulator peptide HH2 for improving anti-tumor immune responses. The CpG-HH2 complex significantly enhanced the production of IFN-γ, TNF-α and IL-1β, promoted the uptake of antigen and strengthened the activation of p38, Erk1/2 and NF-κB in vitro, compared to CpG or HH2 alone. Immunization with NY-ESO-1 antigen plus alum-CpG-HH2 combinatorial adjuvant effectively inhibited tumor growth and reduced tumor burden in prophylactic and therapeutic tumor models and even in passive serum or cellular therapy. In addition, co-administration of NY-ESO-1 with alum-CpG-HH2 combinatorial adjuvant markedly activated NK cell cytotoxicity, induced antibody-dependent cellular cytotoxicity (ADCC), dramatically elicited cytotoxic T lymphocytes (CTLs) response, and increased infiltrating lymphocytes in tumors. Moreover, in vivo depletion of CD8+ T cells completely and depletion of NK cells partially blocked the anti-tumor activity of NY-ESO-1-alum-CpG-HH2 immunization. Overall, our results demonstrate a novel adjuvant combination for cancer vaccine with efficient immunomodulation by stimulating innate immunity and mediating adaptive immunity.


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