Abstract
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.
Highlights
Autologous cellular immunotherapy or immune enhancement therapy has demonstrated some promising benefits for prostate cancer
Our results showed that the prostate cancer stem-like cells (PCSCs)-enriched prostatospheroids expressed significantly higher mRNA and protein levels of both CD44 and EpCAM as compared to their counterpart cells grown under the conventional adherent 2D-culture condition (Fig. 1)
Our results showed that the immunogenic peptidesensitized dendritic cells (DC)-Cytokine-induced killer cell (CIK) cell preparation exhibited significant in vitro cytotoxicity against prostate cancer cells derived from the PCSC-enriched prostatospheroids and antitumor efficacy against the prostatospheroid-derived xenograft tumors
Summary
Autologous 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. ADT is initially efficacious, almost all patients will inevitably develop resistance and metastasis as metastatic castration-resistant prostate cancer (mCRPC) shortly and with a general survival of 2–3 years. Sipuleucel-T (PROVENGE), based on the infusions of CD54+-dendritic cells activated by a recombinant prostatic acid phosphatase-granulocyte-macrophage colony-stimulating factor (PAP-GM-CSF) into patients, is the only FDA-approved immunotherapy for advanced mCRPC [5,6,7]
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