Generation of potent cytotoxic T lymphocytes against in male patients with non-muscle invasive bladder cancer by dendritic cells loaded with dying T24 bladder cancer cells

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Vol. 43 (x): 2017 February 1.[Ahead of print]

doi: 10.1590/S1677-5538.IBJU.2016.0274


ORIGINAL ARTICLE

Eu Chang Hwang 1,2, Seung Il Jung 2, Hyun-Ju Lee 1, Je-Jung Lee 1,3,4,5, Dong Deuk Kwon 2
1 Research Center for Cancer Immunotherapy, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; 2 Department of Urology and 3 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo, Republic of Korea; 4 Vaxcell-Bio Therapeutics, Hwasun, Jeollanamdo, Republic of Korea; 5 The Brain Korea 21 Project, Center forBiomedical Human Resources at Chonnam National University, Gwangju, Republic of Korea

ABSTRACT

Background: In order to induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)-based immunotherapy for bladder cancer, various tumor antigens can be loaded onto DCs.
Objective: The aim of this study was to establish a method of immunotherapy for male patients with non-muscle invasive bladder cancer (NMIBC), using bladder cancer-spe¬cific CTLs generated in vitro by DCs.
Materials and Methods: Monocyte-derived DCs from bladder cancer patients were in¬duced to mature in a standard cytokine cocktail (IL-1β, TNF-α, IL-6, and PGE2: standard DCs, sDCs) or anα-type 1-polarized DC (αDC1) cocktail (IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid) and loaded with the UVB-irradiated bladder cancer cell line, T24. Antigen-loaded αDC1s were evaluated by morphological and functional assays, and the bladder cancer-specific CTL response was analyzed by cytotoxic assay.
Results: The αDC1s significantly increased the expression of several molecules pertain¬ing to DC maturation, regardless of whether or not the αDC1s were loaded with tumor antigens, relative to sDCs. The αDC1s demonstrated increased production of interleukin-12 both during maturation and after subsequent stimulation with CD40L that was not significantly affected by loading with tumor antigens as compared to that of sDCs. Bladder cancer-specific CTLs targeting autologous bladder cancer cells were success¬fully induced by αDC1s loaded with dying T24 cells.
Conclusion: Autologous αDC1s loaded with an allogeneic bladder cancer cell line re¬sulted in increased bladder cancer-specific CTL responses as compared to that with sDCs, and therefore, may provide a novel source of DC-based vaccines that canbe used in immunotherapy for male patients with NMIBC.

Keywords: Dendritic Cells; Urinary Bladder Neoplasms; T-Lymphocytes, Cytotoxic

 

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