Improved efficacy of therapeutic vaccination with dendritic cells pulsed with tumor cell lysate against hepatocellular carcinoma by introduction of 2 tandem repeats of microbial HSP70 peptide epitope 407-426 and OK-432.
Therapeutic vaccination with dendritic cells (DCs) pulsed with tumor cell lysate vaccine (H-D) represents an attractive approach for hepatocellular carcinoma (HCC) treatment. However, the efficacy of this approach is not most satisfactory for the low levels of T helper 1 (Th1)-type cytokines secretion and weak T cell responses. In this study, in order to increase the potency of H-D, two tandem repeats of microbial HSP70 peptide epitope 407-426 (2mHSP70(407-426), M2) which has been demonstrated to be effective in enhancing DC maturation were applied. The DC vaccine (HM-D) which was HCC tumor cell lysate pulsed with M2 was developed. Nevertheless, the immunotherapeutic effect was still not satisfactory enough even some promotion was obtained. Therefore, OK-432 (OK), which is a useful anti-cancer agent and effectively in stimulating DC maturation, was introduced to HM-D. Our results demonstrated that treatment with the improved DC vaccine which was tumor cell lysate pulsed with M2 and OK (HMO-D), compared with H-D and HM-D, significantly increased cell surface markers (MHC-I and II, CD40, CD80, CD86 and CD11c) expression on DCs, enhanced Th1-type cytokines (IL-12, TNF-α and IFN-γ) production but not Th2-type cytokine (IL-5) production, induced remarkable high levels of lymphocytes proliferation and CD8(+) cytotoxic T-lymphocyte (CTL). Furthermore, immunization with HMO-D effectively reduced tumor progression and enhanced the survival of mice with H22 tumors. Besides, we also found that the capability of M2 in inducing the Th1 cytokines was stronger than OK. In view of these results, HMO-D vaccination provided a novel immunotherapeutic approach for the treatment of HCC.
Minigene Pharmacy Laboratory, School of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China.
Chiyu
C
Ge
Yun
Y
Xing
Qi
Q
Wang
Wen
W
Xiao
Yong
Y
Lu
Xiangbing
X
Hu
Zhenqiu
Z
Gao
Maolei
M
Xu
Yanjun
Y
Ma
Rongyue
R
Cao
Jingjing
J
Liu
D000818:Animals; D019496:Cancer Vaccines / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000628:therapy*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D000939:Epitopes / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D008114:Liver Neoplasms, Experimental / Q000628:therapy*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010844:Picibanil / Q000276:immunology / Q000627:therapeutic use*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D020080:Tandem Repeat Sequences; D016896:Treatment Outcome
D019496:Cancer Vaccines; D016207:Cytokines; D000939:Epitopes; D018840:HSP70 Heat-Shock Proteins; D010844:Picibanil