Drug name: Dendritic Cell-Based Vaccines


Related CSCTT Targets

CD24+/CD44+ Melanoma cells [ref.1]

Introduction

Dendritic cells (DCs) are the most effective antigen-presenting cells (APCs) in the human immune system. DCs initiate immunity by the activation of naive B and T cells — the effector cells of the adaptive immune system — and by the stimulation of natural killer cells — the crucial cellular instigators of innate resistance. Besides linking innate and adaptive immunity, DCs additionally control immunity through their ability to induce antigen-specific unresponsiveness of lymphocytes in primary and secondary lymphoid tissues by mechanisms that include deletion and induction of regulatory cells[1,2].
Figure from Wikipedia
Tumor vaccines can be divided into two broad categories – peptide-based vaccines and cell-based vaccines – as determined by the immunogen used in the vaccine (peptide vs cells)[3,4].

DCs acquire, process, and present antigens to T-cells, and provide the stimulatory signals and cytokines required to induce T-cells to proliferate and differentiate into effector cells. For this reason, infusion of in vitro-generated antigen-loaded DCs cells has been investigated as a vaccination strategy to elicit T-cell-mediated responses, particularly in the context of cancer where DC function in vivo is often blunted or subverted by factors released by the tumor[5].

Various DC antigen-loading strategies have been tested to date. Prominent among in vitro methodologies is the loading of DCs with tumor-derived peptides (Figdor et al. 2004 ), or cellular material from lysates or irradiated tissue. It is also possible to transduce DCs with autologous tumor-derived messenger (m)RNA or DNA (Shurin et al. 2010 ) or to directly fuse DCs with autologous tumor cells (Lee 2011; Shu et al. 2007) [5].

Cell-based vaccines are not HLA-restricted and elicit an immune response against a broad spectrum of antigens that are expressed by the target cells, although often these vaccines elicit only a narrow immune response against very few epitopes, a phenomenon known as epitope dominance.

[1] Hackstein, H. and A. W. Thomson (2004). "Dendritic cells: emerging pharmacological targets of immunosuppressive drugs." Nature Reviews Immunology 4(1): 24-34.
[2] Vik-Mo, E. O., M. Nyakas, B. V. Mikkelsen, M. C. Moe, P. Due-Tonnesen, E. M. Suso, S. Saeboe-Larssen, C. Sandberg, J. E. Brinchmann, E. Helseth, A. M. Rasmussen, K. Lote, S. Aamdal, G. Gaudernack, G. Kvalheim and I. A. Langmoen (2013). "Therapeutic vaccination against autologous cancer stem cells with mRNA-transfected dendritic cells in patients with glioblastoma." Cancer Immunol Immunother 62(9): 1499-1509.
[3] Zhou, L., L. Lu, M. S. Wicha, A. E. Chang, J. C. Xia, X. Ren and Q. Li (2015). "Promise of cancer stem cell vaccine." Hum Vaccin Immunother 11(12): 2796-2799.
[4] Alatrash, G. and J. J. Molldrem (2011). "Vaccines as consolidation therapy for myeloid leukemia." Expert Rev Hematol 4(1): 37-50.
[5] Gasser, O. and I. F. Hermans (2015). "Dendritic Cell-Based Vaccines." Subunit Vaccine Delivery. C. Foged, T. Rades, Y. Perrie and S. Hook. New York, NY, Springer New York: 243-257.

Dendritic Cell-Based Vaccines Schema

...

Reference

  • [1] Dendritic cell based immunotherapy using tumor stem cells mediates potent antitumor immune responses.
    Dashti, A., et al. (2016). Cancer Lett 374(1): 175-185. [ 26803056 ]

Back to top