MF59 formulated with CpG ODN as a potent adjuvant of recombinant HSP65-MUC1 for inducing anti-MUC1+ tumor immunity in mice.

MF59 is an oil-in-water emulsion adjuvant approved for influenza vaccines for human use in Europe. Due to its Th2 inducing properties, MF59 is seldom tested for cancer vaccines. In this study, MF59 formulated with a C-type CpG oligodeoxynucleotide (YW002) was tested for its Th1 adjuvant activity to induce immune responses to HSP65-MUC1, a recombinant fusion protein incorporating a mycobacterial heat shock protein (HSP65) and mucin 1, cell surface associated (MUC1) derived peptide. Combination of YW002 with MF59 (MF59-YW002) could confer a potent Th1 biasing property to the adjuvant, which enhanced the immunogenicity of HSP65-MUC1 to induce significantly higher levels of specific IgG2c, increased IFN-γ mRNA expression in splenocytes and the generation of antigen-specific cytotoxic T lymphocytes in mice. When prophylactically applied, MF59-YW002 adjuvant containing HSP65-MUC1 inhibited the growth of MUC1+ B16 melanoma and prolonged the survival of tumor-bearing mice. In contrast, adjuvant containing MF59 with HSP65-MUC1 in the absence of YW002, promoted the growth of MUC1+ B16 melanoma in mice. These results suggest that MF59 plus CpG oligodeoxynucleotide might be developed as an efficient adjuvant for tumor vaccines against melanoma, and possibly other tumors.

Yang M ，Yan Y ，Fang M ，Wan M ，Wu X ，Zhang X ，Zhao T ，Wei H ，Song D ，Wang L ，Yu Y ... -  《-》

Heat shock fusion protein induces both specific and nonspecific anti-tumor immunity.

Li D ，Li H ，Zhang P ，Wu X ，Wei H ，Wang L ，Wan M ，Deng P ，Zhang Y ，Wang J ，Liu Y ，Yu Y ，Wang L ... -  《EUROPEAN JOURNAL OF IMMUNOLOGY》

Anti-PD1 antibody enhances the anti-tumor efficacy of MUC1-MBP fusion protein vaccine via increasing Th1, Tc1 activity and decreasing the proportion of MDSC in the B16-MUC1 melanoma mouse model.

In previous studies, we have obtained a notable anti-tumor efficacy of the recombinant MUC1-MBP vaccine in the process of mouse B16-MUC1 melanoma treatment. However, the tumor cannot be eliminated completely. We found that the tumor inhibition rate decreased from 81.67% (five immunizations) to 43.67% (eight immunizations) after more than five immunizations, indicating persistent vaccine stimulation may activate immunosuppressive factors. In the present study, we revealed that programmed cell death 1 (PD1), an inhibitory molecule suppressing T cell function, expressed on splenic and tumor-infiltrating T cells were up-regulated by the vaccine. Therefore, to optimize the anti-tumor efficacy of the vaccine, we employed combination immunotherapy with MUC1-MBP vaccine and αPD1 (anti-PD1 antibody). Results showed that combination immunotherapy induced a more remarkable anti-tumor efficacy, the tumor clearance being increased to 80% from 20% which obtain by MUC1-MBP vaccine immunizations. To investigate the possible underlying mechanism, IFN-γ secretion and cytotoxic T lymphocyte (CTL) cytotoxicity were measured by enzyme-linked immunosorbent assay (ELISA) and xCELLigence real-time cell analyzer (RTCA) respectively. T cell subsets and immunosuppressive cells in the mouse spleen and tumor microenvironment were analyzed by FACS. Results showed that the proportion of splenic CD8+T cells and tumor infiltration was increased and the activity of CTL killing, T helper 1 (Th1), Type 1 CD8+T (Tc1) was enhanced, indicating that the anti-tumor efficacy enhanced by combination immunotherapy was mainly through boosting CD8+T cells mediated anti-tumor cellular immunity. Additionally, combination immunotherapy significantly decreased the splenic and tumor-infiltrating myeloid derived suppressor cells (MDSCs). These results demonstrated that combination immunotherapy with MUC1-MBP vaccine and αPD1 was capable to invoke a more potent anti-tumor immune response and provide a foundation for further research.

Zhang Z ，Zhou H ，Liu Y ，Ren J ，Wang J ，Sang Q ，Lan Y ，Wu Y ，Yuan H ，Ni W ，Tai G ... -  《-》

A CpG oligodeoxynucleotide potentiates the anti-tumor effect of HSP65-Her2 fusion protein against Her2 positive B16 melanoma in mice.

Although being promising tumor vaccine candidates in animal models, heat shock protein (HSP)-based tumor vaccines have not yet succeeded in the clinical trials, implying the necessity to be formulated with appropriate adjutants to enhance their immunogenicity. In this study, we investigated whether a B-class CpG ODN (BW006), a TLR9 agonist, could facilitate HSP65-Her2, a recombinant protein between mycobacterial HSP65 and Her2-derived peptide, to induce vigorous anti-tumor activity against Her2 positive tumors in mice both prophylactically and therapeutically. It was found that BW006 could enhance prophylactic and therapeutic effect of HSP65-Her2 with improved survival of the mice bearing Her2(+) B16 melanoma and HSP65-Her2 specific Th1 response.

Yan Y ，Cao Z ，Yang M ，Li H ，Wei H ，Fu Y ，Song D ，Wang L ，Yu Y ... -  《-》

MUC1 and maltose‑binding protein recombinant fusion protein combined with Bacillus Calmette‑Guerin induces MUC1‑specific and nonspecific anti‑tumor immunity in mice.

Fang F ，Ma J ，Ni W ，Wang F ，Sun X ，Li Y ，Li Q ，Xie F ，Wang J ，Zhai R ，Liu Z ，Gao S ，Tai G ... -  《-》