Dendritic cells (DCs) play a primary role in antigen presentation to CD4 and CD8 T cells and induce acquired immune response against cancer cells. Therefore, determining positive modulators of DC activation to improve therapeutic approaches for cancer immunotherapy is greatly needed. In this study, we investigated the effect of maitake α-glucan YM-2A, isolated from Grifola frondosa, on the maturation and function of DCs and its adjuvant effect on a tumor-associated antigen (TAA)-loaded DC vaccine against murine tumor. We showed that YM-2A induced morphological changes and increased cell-surface maturation markers and cytokine production in DCs. In a mixed lymphocyte reactions assay, YM-2A-treated DCs increased proliferation and production of IFN-γ by allogeneic CD4 and CD8 T cells. These results indicate that YM-2A phenotypically and functionally activates DCs. Furthermore, YM-2A-treated TAA-loaded DC vaccine significantly reduced tumor growth and improved survival in two murine tumor models, CT-26 tumor-bearing BALB/c mice and B16 melanoma-bearing C57BL/6 mice. YM-2A-treated TAA-loaded DC vaccine increased splenic IFN-γ producing CD4 and CD8 T cells in CT-26 tumor-bearing BALB/c mice. Antibody neutralization studies indicated that YM-2A-induced DC maturation is mediated, in part, by the Dectin-1-dependent pathway. Overall, YM-2A-treatment with a TAA-loaded DC vaccine could be an excellent candidate for immunotherapy against cancer.
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http://dx.doi.org/10.1016/j.intimp.2018.12.039 | DOI Listing |
Int Immunopharmacol
February 2019
Department of Microbial Chemistry, Kobe Pharmaceutical University, Kobe, Japan. Electronic address:
Cancer Gene Ther
July 2017
Division of Translational Research for Biologics, Department of Internal Related Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Recently, the US FDA approved sipuleucel-T, which is composed of autologous DCs stimulated with a recombinant fusion protein of prostatic acid phosphatase (PAP) and granulocyte-macrophage colony-stimulating factor (GM-CSF), as the first immunotherapeutic agent for metastatic castration resistant prostate cancer (mCRPC). However, sipuleucel-T demonstrated only modest efficacy in mCPRC patients. Researchers are now investigating the potential of p53 protein as a tumor-associated antigen (TAA) loaded in DC-based cancer vaccine.
View Article and Find Full Text PDFOncoimmunology
September 2013
Seta Clinic; Tokyo, Japan.
The addition of zoledronate to tumor-associated antigen (TAA)-loaded dendritic cells (DCs) promotes the activation of interferon γ-secreting Vγ9 γδ T cells, in turn eliciting TAA-specific CD8 T-cell responses. Immunological responses induced by zoledronate-pulsed DC-based vaccines have been associated with therapeutic effects in clinical trials.
View Article and Find Full Text PDFCancer Immunol Immunother
February 2003
The Cancer Center of Long Island, Stony Brook, NY, USA.
Dendritic cells (DC) loaded with tumor associated antigens (TAA) are often used for the vaccination of cancer patients; however methodologies for the vaccine preparation have not yet been standardized. The purpose of this work was to optimize the ex-vivo production of functional TAA-loaded DC that would produce interleukin-2 (IL-12) and enhance the T cell response. We generated ex-vivo DC from human monocytes with granulocyte macrophage-colony stimulating factor (GM-CSF) and IL-4, and whole necrotic tumor cells (cell lysates) of cancer cell lines were used as model TAA.
View Article and Find Full Text PDFJ Soc Biol
October 2001
Unité de thérapie cellulaire et moléculaire, Département d'immunologie-hématologie-transfusion, université libre de Bruxelles (ULB).
In cancer immunotherapy, the use of dendritic cells (DC) loaded with tumor-associated antigens (TAA) emerged as a promising strategy. We initiated 3 pilot clinical trials with immunological endpoints using TAA loaded autologous DC. These trials showed that this approach was safe and associated with the induction of potent TAA specific IFN-gamma responses, which were transient despite the providing a further help through KLH presentation.
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