Tumor growth inhibition by mSTEAP peptide nanovaccine inducing augmented CD8+ T cell immune responses
Poly(lactic-co-glycolic) acid (PLGA) has been successfully used in drug delivery and biomaterial applications, but very little attention has been directed towards the potential in vivo effects of peptide-loaded PLGA nanoparticles (NPs), specifically the potency of intravenous (IV) STEAP peptide-loaded PLGA-NP (nanovaccine) dosing and whether STEAP-specific CD8+ T cells directly play a key role in tumor inhibition. To address these concerns, syngeneic prostate cancer mouse models were established and treated with either mSTEAP peptide emulsified in incomplete Freund’s adjuvant (IFA) via subcutaneous (SC) injection or mSTEAP peptide nanovaccine containing the same amount of peptide via IV or SC injection. Meanwhile, mice were treated with either CD8b mAb followed by nanovaccine treatment, free mSTEAP peptide, or empty PLGA-NPs. Immune responses in these mice were examined using cytotoxicity assays at 14 days after treatment. Tumor size and survival in various treatment groups were measured and monitored. The results demonstrated that mSTEAP peptide nanovaccine resulted in tumor inhibition by eliciting a significantly stronger CD8+ T cell immune response when compared with the controls. Moreover, the survival periods of mice treated with mSTEAP nanovaccine were significantly longer than those of mice treated with mSTEAP peptide emulsified in IFA or the treatment controls. Additionally, it was observed that the peptide nanovaccine was mainly distributed in the mouse liver and lungs after IV injection. These findings suggest that the peptide nanovaccine is a promising immunotherapeutic approach and offers a new opportunity for prostate cancer therapies.
KeywordsAntigenic peptide Poly(lactide-co-glycolide) acid Nanovaccine Antigen-presenting cells Cancer immunotherapy
Cytotoxic T lymphocyte
Incomplete Freund’s adjuvant
Major histocompatibility complex
Mouse six-transmembrane epithelial antigen of the prostate
Scanning electron microscope
Transgenic adenocarcinoma of the mouse prostate
This work was supported by the grants from the Natural Science Foundation of Zhejiang, China (LY14H160015), to WM and the US Department of Defense (PC041024) to BM.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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