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

// Yaomei Tian 1, * , Meng Li 2, * , Chaoheng Yu 1 , Rui Zhang 1 , Xueyan Zhang 1 , Rong Huang 1 , Lian Lu 1 , Fengjiao Yuan 1 , Yingzi Fan 1 , Bailing Zhou 1 , Ke Men 1 , Heng Xu 1 and Li Yang 1 1 State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, Sichuan, China 2 Chengdu Blood Center, Chengdu, Sichuan, China * These authors contributed equally to this work Correspondence to: Li Yang, email: yl.tracy73@gmail.com 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.