Background: The antigen HCA587 (also known as MAGE-C2), which is considered a cancer-testis antigen, exhibits upregulated expression in a wide range of malignant tumors with unique immunological properties, and may thus serve as a promising target for tumor immunotherapy.
Objective: The study aimed to explore the antitumor effect of the HCA587 protein vaccine and the response of humoral and cell-mediated immunity.
Methods: The HCA587 protein vaccine was formulated with adjuvants CpG and ISCOM. B16 melanoma cells were subcutaneously inoculated to C57BL/6 mice, followed by treatment with HCA587 protein vaccine subcutaneously. Mouse survival was monitored daily, and tumor volume was measured every 2 to 3 days. The tumor sizes, survival time and immune cells in tumor tissues were detected. And the vital immune cell subset and effector molecules were explored.
Results: After treatment with HCA587 protein vaccine, the vaccination elicited significant immune responses, which delayed tumor growth and improved animal survival. The vaccination increased the proportion of CD4+ T cells expressing IFN-γ and granzyme B in tumor tissues. The depletion of CD4+T cells resulted in an almost complete abrogation of the antitumor effect of the vaccination, suggesting that the antitumor efficacy was mediated by CD4+ T cells. In addition, knockout of IFN-γ resulted in a decrease in granzyme B levels, which were secreted by CD4+ T cells, and the antitumor effect was also significantly attenuated.
Conclusion: The HCA587 protein vaccine may increase the levels of granzyme B expressed by CD4+ T cells, and this increase is dependent on IFN-γ, and the vaccine resulted in a specific tumor immune response and subsequent eradication of the tumor.
[http://dx.doi.org/10.1007/s00262-020-02503-0] [PMID: 32034426]
[http://dx.doi.org/10.1111/j.1349-7006.2009.01303.x] [PMID: 19719775]
[http://dx.doi.org/10.4049/jimmunol.169.2.1102] [PMID: 12097419]
[http://dx.doi.org/10.1097/01.LAB.0000080605.73839.96] [PMID: 12920247]
[http://dx.doi.org/10.1002/ijc.23966] [PMID: 18942708]
[http://dx.doi.org/10.1038/sj.bjc.6690810] [PMID: 10576668]
[http://dx.doi.org/10.1111/j.1440-1746.2006.04271.x] [PMID: 16872310]
[http://dx.doi.org/10.1111/j.0300-9475.2004.01503.x] [PMID: 15541044]
[http://dx.doi.org/10.1073/pnas.0707140104] [PMID: 18216244]
[http://dx.doi.org/10.1007/s00262-008-0603-5] [PMID: 18941744]
[http://dx.doi.org/10.4049/jimmunol.1301633] [PMID: 24293627]
[http://dx.doi.org/10.1038/ni.2523] [PMID: 23334788]
[http://dx.doi.org/10.1084/jem.20121190] [PMID: 23547098]
[http://dx.doi.org/10.1084/jem.20091918] [PMID: 20156971]
[http://dx.doi.org/10.4049/jimmunol.1101244] [PMID: 21880986]
[http://dx.doi.org/10.1080/2162402X.2016.1171445] [PMID: 27471650]
[http://dx.doi.org/10.1158/2326-6066.CIR-13-0068] [PMID: 24396833]
[http://dx.doi.org/10.1111/j.0105-2896.2010.00907.x] [PMID: 20536556]
[http://dx.doi.org/10.1080/15384047.2015.1078027] [PMID: 26391871]
[http://dx.doi.org/10.1158/0008-5472.CAN-15-1085] [PMID: 26719533]
[http://dx.doi.org/10.3389/fimmu.2016.00072] [PMID: 26973649]
[http://dx.doi.org/10.18632/oncotarget.14365] [PMID: 28052005]