Abstract
Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.
Highlights
Despite significant advances in cancer therapy, such as surgical techniques, radiotherapy, and systemic therapy including immune checkpoint inhibitors [1,2,3,4,5,6], it remains extremely challenging to treat advanced cancers with organ involvement and distant metastasis.Vaccines 2019, 7, 120; doi:10.3390/vaccines7030120 www.mdpi.com/journal/vaccinesManufacturing technology for antigen-presenting cell (APC)-based immunotherapy is being developed using active dendritic cells (DCs), the most potent APCs of the immune system, for therapeutic vaccination against cancer
The objective of this study was to address the effectiveness of recombinant human granulocyte colony-stimulating factor (rhG-CSF) administration and how it might affect the manufacture of DC-based vaccines for clinical use in cancer immunotherapy
The statistical significance of the mature DCs (mDCs) product was dependent on the number of apheresed monocytes because the DC yield varied from a few DCs to a large amount, even when the standard operating procedure was applied at a single institute
Summary
Manufacturing technology for antigen-presenting cell (APC)-based immunotherapy is being developed using active dendritic cells (DCs), the most potent APCs of the immune system, for therapeutic vaccination against cancer. APC-based immunotherapy with active DCs has been reported for the induction of effective immunity against cancer antigens [7]. It is possible that the immune checkpoints on the DCs would interfere with the response of antitumor immunity. Immune DCs are generated from peripheral monocytes expressing tumor-specific antigens and have been applied in active immunotherapy against cancers [9,10], which requires large-scale ex vivo generation of homogeneous, mature, and functional DCs. Cancer vaccines containing autologous monocyte-derived mature DCs (mDCs) are conventionally manufactured using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-4 and are principally targeted against a specific antigen. The efficacy of DC-based immunotherapy is more demonstrated by the delayed separation of the survival curve with a benefit in terms of prolonged overall survival rather than conventional evaluation approaches such as the use of the response rates [13,15,19]
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