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.