Journal
STEM CELL RESEARCH & THERAPY
Volume 11, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13287-020-01634-6
Keywords
Prostate cancer stem-like cells; Dendritic cells; Cytokine-induced killer cells; Cellular immunotherapy; Cell membrane antigen
Funding
- Innovation and Technology Fund [GHP/003/16GD]
- Innovation and Technology Commission of Hong Kong [InP/260/16, InP/270/16]
- National Natural Science Foundation of China [81802566]
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BackgroundAutologous cellular immunotherapy or immune enhancement therapy has demonstrated some promising benefits for prostate cancer. T cell-based immunotherapy or sipuleucel-T therapy has yielded certain beneficial responses and a slight improvement on the overall survival of patients with metastatic castration-resistant prostate cancer (mCRPC) as shown in some clinical trials, suggesting that prostate cancer is immunoresponsive.MethodsIn this study, we developed an adaptive cytokine-induced killer cell (CIK)-based immunotherapeutic application targeting the prostate cancer stem-like cells (PCSCs). In this therapeutic platform, dendritic cells (DC) were isolated from the peripheral blood mononuclear cells (PBMCs) and preloaded or sensitized with immunogenic peptides derived from two PCSC-associated cell membrane molecules, CD44 and EpCAM, followed by co-culture with the expanded peripheral blood lymphocyte (PBL)-derived CIK cells. The in vitro cytotoxic activity of DC-activated CIK cells against PCSCs was determined by CCK8 and TUNEL assays, and the in vivo anti-tumor effect of DC-activated CIK cells on prostate cancer xenograft tumors was evaluated in subcutaneous and orthotopic xenograft models.ResultsOur results showed that the peptide-sensitized DC-CIK cell preparation manifested significant in vitro cytotoxic activity against the PCSC-enriched prostatospheroids and also in vivo anti-tumor effect against prostate cancer xenografts derived from the PCSC-enriched prostatospheroids.ConclusionsTogether, our established immunogenic peptide-sensitized DC-CIK-based cell preparation platform manifests its potential immunotherapeutic application in targeting the PCSCs and also prostate cancer.
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