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Drug Delivery and Translational Research

, Volume 9, Issue 6, pp 1095–1105 | Cite as

Tumor growth inhibition by mSTEAP peptide nanovaccine inducing augmented CD8+ T cell immune responses

  • Qiuqiang Chen
  • Ying Bao
  • Danielle Burner
  • Sharmeela Kaushal
  • Yu Zhang
  • Theresa Mendoza
  • Michael Bouvet
  • Cengiz Ozkan
  • Boris MinevEmail author
  • Wenxue MaEmail author
Original Article

Abstract

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.

Keywords

Antigenic peptide Poly(lactide-co-glycolide) acid Nanovaccine Antigen-presenting cells Cancer immunotherapy 

Abbreviations

APC

Antigen-presenting cells

CTL

Cytotoxic T lymphocyte

DC

Dendritic cell

IFA

Incomplete Freund’s adjuvant

IP

Intraperitoneal injection

IV

Intravenous injection

MHC

Major histocompatibility complex

mSTEAP

Mouse six-transmembrane epithelial antigen of the prostate

NP

Nanoparticle

PLGA

Poly(lactic-co-glycolic) acid

SC

Subcutaneous injection

SEM

Scanning electron microscope

TRAMP

Transgenic adenocarcinoma of the mouse prostate

Notes

Funding information

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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Copyright information

© Controlled Release Society 2019

Authors and Affiliations

  1. 1.Key Laboratory for Translational MedicineThe First Affiliated Hospital of Huzhou University School of MedicineHuzhouChina
  2. 2.Department of Clinical MedicineHuzhou University School of MedicineHuzhouChina
  3. 3.Department of Medicine and Moores Cancer CenterUniversity of California San DiegoLa JollaUSA
  4. 4.Materials Science and Engineering Program, Department of Mechanical EngineeringUniversity of California RiversideRiversideUSA
  5. 5.Mechanical and Automotive Engineering, School of EngineeringRMIT UniversityMelbourneAustralia
  6. 6.Calidi BiotherapeuticsSan DiegoUSA

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