Abstract
Dendritic cell cancer vaccines have already become a treatment modality for patients with various cancer types. However, the curative potential of this immunotherapy is limited by the existence of negative feedback mechanisms that control dendritic cells (DCs) and T-cell function. By inhibiting the expression of inhibitory factors using RNA interference technology, a new generation of DC vaccines was developed. Vaccine-stimulated T cells showed antitumor effects both in vitro and in cancer patients. Here, we describe the development and validation of a fully GMP-compliant production process of ex vivo DC cancer vaccines combined with the blockade of immunosuppressive pathways using small interfering RNAs. The protocol can be used for DC-based therapy for all cancer types.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Steinman RM, Banchereau J (2007) Taking dendritic cells into medicine. Nature 449:245–252
Hoos A, Britten CM, Huber C, O’Donnell-Tormey J (2011) A methodological framework to enhance the clinical success of cancer immunotherapy. Nat Biotechnol 29:867–870
Munn DH, Sharma MD, Lee JR, Jhaver KG, Johnson TS et al (2002) Potential regulatory function of human dendritic cells expressing indoleamine 2,3-dioxygenase. Science 297:1867–1870
Hwu P, Du MX, Lapointe R, Do M, Taylor M-W, Young HA (2000) Indoleamine 2,3-dioxygenase production by human dendritic cells results in the inhibition of T cell proliferation. J Immunol 164:3596–3599
Braun D, Longman RS, Albert ML (2005) A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic cell maturation. Blood 106:2375–2381
Munn DH, Sharma MD, Hou D (2004) Expression of indoleamine 2,3-dioxygenase by plasmacytoid dendritic cells in draining-draining lymph nodes. J Clin Invest 114:280–290
Jonuleit H, Schmitt E, Stenbrink K, Enk AH (2001) Dendritic cells as a tool to induce anergic and regulatory T cells. Trends Immunol 22:394–400
Sioud M (2019) Releasing the immune system brakes using siRNAs enhances cancer immunotherapy. Cancers 11, cancers11020176
Sioud M (2011) Promises and challenges in developing RNAi as a research tool and therapy. Methods Mol Biol 703:173–187
Flatekval GF, Sioud M (2010) Modulation of dendritic cell function and maturation with mono- and bifunctional small interfering RNAs targeting indoleamine 2,3-dioxygenase. Immunology 128:e837–e848
Sioud M, Saebøe-Larssen S, Hetland TE, Kaern J, Mobergslien A, Kvalheim G (2013) Silencing of indoleamine 2,3-dioxygenase enhances dendritic cell immunogenicity and antitumour immunity in cancer patients. Int J Oncol 43:280–288
Acknowledgments
This work was supported by the Norwegian Cancer Society.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
Sæbøe-Larssen, S., Sioud, M. (2020). Improving Dendritic Cell Cancer Vaccine Potency Using RNA Interference. In: Sioud, M. (eds) RNA Interference and CRISPR Technologies. Methods in Molecular Biology, vol 2115. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0290-4_14
Download citation
DOI: https://doi.org/10.1007/978-1-0716-0290-4_14
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-0289-8
Online ISBN: 978-1-0716-0290-4
eBook Packages: Springer Protocols