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

Abstract

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.

The adenylyl cyclase Rv2212 modifies the proteome and infectivity of Mycobacterium bovis BCG

“…4 and Tables 2 and 3), are highly immunogenic proteins. These two proteins have been extensively used in the formulation of adjuvants (Li et al 2010;Yang et al 2012). Interestingly, the sole use of a plasmid encoding groEL-2 gene can confer the same degree of protection as live BCG against tuberculosis (Silva et al 1999).…”

Vaccine adjuvants as potential cancer immunotherapeutics

“…Yet the use of MF59 is limited for cancer vaccines, as it can induce not only the advantageous T h 1-type responses but also the undesired T h 2-type immune responses for anti-tumor immunity. However, the combination of MF59 with CpG ODN has been reported to induce melanoma-specific anti-tumor immune responses and prolong the survival of tumor-bearing mice in a mouse melanoma model when used as an adjuvant in the therapeutic cancer vaccine ( 51 ).…”

Chitin, Chitosan, and Glycated Chitosan Regulate Immune Responses: The Novel Adjuvants for Cancer Vaccine

“…Several novel adjuvants are licensed for human use in different countries, including aluminum salts, squalene-oil-water emulsion (MF-59), monophosphoryl lipid (MPL) A and virosomes [19, 20]. However, it is still in great need to invent novel adjuvant for clinical practice.…”