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Abstract
PurposeMalignant melanoma’s (MM) incidence is rising faster than that of any other cancer in the US and the overall survival at 5 years is less than 10%. B cell associated protein 31 (BAP31) is overexpressed in most MMs and might be a promising target for immunotherapy of this disease.Experimental designFirstly, we investigated the expression profiles of human BAP31 (hBAP31) and mouse BAP31 (mBAP31) in human and mouse normal tissues, respectively. The expression level of hBAP31 in human MMs and mBAP31 in B16 melanoma cells was also analyzed. Then we constructed novel mBAP31 DNA vaccines and tested there ability to stimulate mBAP31-specific immune responses and antitumor immunity in B16 melanoma-bearing mice.ResultsFor the first time, we found that protein expression of hBAP31 were dramatically upregulated in human MMs when compared with human normal tissues. Predominant protein expression of mBAP31 was found in mouse B16 melanoma cells but not in mouse important organs. When mice were immunized with mBAP31 DNA vaccines, strong cellular response to mBAP31 was observed in the vaccinated mice. CTLs isolated from immunized mice could effectively kill mBAP31-positive target mouse B16 melanoma tumor cells in vitro and vaccination with mBAP31 DNA vaccines had potent anti-tumor activity in therapeutic model using B16 melanoma cells.ConclusionsThese are the first data supporting a vaccine targeting BAP31 that is capable of inducing effective immunity against BAP31-expressing MMs and will be applicable to human MMs and hBAP31 DNA vaccine warrants investigation in human clinical trials.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0153-6) contains supplementary material, which is available to authorized users.
Highlights
Cancer malignancies are among the most life-threatening diseases worldwide [1]
Predominant protein expression of mouse BAP31 (mBAP31) was found in mouse B16 melanoma cells but not in mouse important organs
When mice were immunized with mBAP31 DNA vaccines, strong cellular response to mBAP31 was observed in the vaccinated mice
Summary
Protein expression profiles of hBAP31 in human MMs To assess the protein expression levels of hBAP31 in MMs, we employed IHC analysis using mAbs against hBAP31 established in our lab [18]. We identified high protein expression level of hBAP31 in human MM tissues, with a total positive rate of 86.5% These results suggested that hBAP31 might be a promisingly attractive vaccine target for human MMs. our preliminary work suggested that depletion of BAP31 has a negative impact on the proliferation of tumor cells, indicating that BAP31 may play an important role in tumorigenesis. No autoimmune disorders were observed in the vaccinated mice, suggesting the safety of vaccination with mBAP31 DNA vaccine These are the first data supporting a vaccine targeting BAP31 that will be applicable to human MMs. In conclusion, we demonstrated that immunization with a novel LAMP-mBAP31 chimera DNA vaccine can successfully generate mBAP31-specific anti-tumor immunity in mice supports further evaluation regarding the promising clinical efficacy of this vaccine and the preclinical trials is ongoing in our lab.
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