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RNA Therapeutics pp 403–450Cite as

Immunotherapy of Cancer with Dendritic Cells Loaded with Tumor Antigens and Activated Through mRNA Electroporation

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 629))

Abstract

Since decades, the main goal of tumor immunologists has been to increase the capacity of the immune system to mediate tumor regression. Considerable progress has been made in enhancing the efficacy of therapeutic anticancer vaccines. First, dendritic cells (DCs) have been identified as the key players in orchestrating primary immune responses. A better understanding of their biology and the development of procedures to generate vast amounts of DCs in vitro have accelerated the development of potent immunotherapeutic strategies for cancer. Second, tumor-associated antigens have been identified which are either selectively or preferentially expressed by tumor cells and can be recognized by the immune system. Finally, several studies have been performed on the genetic modification of DCs with tumor antigens. In this regard, loading the DCs with mRNA, which enables them to produce/process and present the tumor antigens themselves, has emerged as a promising strategy. Here, we will first overview the different aspects that must be taken into account when generating an mRNA-based DC vaccine and the published clinical studies exploiting mRNA-loaded DCs. Second, we will give a detailed description of a novel procedure to generate a vaccine consisting of tumor antigen-expressing dendritic cells with an in vitro superior capacity to induce anti-tumor immune responses. Here, immature DCs are electroporated with mRNAs encoding a tumor antigen, CD40 ligand (CD40L), CD70, and constitutively active (caTLR4) to generate mature antigen-presenting DCs.

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Authors and Affiliations

  1. Laboratory of Molecular and Cellular Therapy, Department of Physiology – Immunology, Medical School of the Vrije Universiteit Brussel (VUB), Brussels, Belgium

    An M.T. Van Nuffel, Jurgen Corthals, Bart Neyns, Carlo Heirman, Kris Thielemans & Aude Bonehill

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  1. An M.T. Van Nuffel
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  2. Jurgen Corthals
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  3. Bart Neyns
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  4. Carlo Heirman
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  5. Kris Thielemans
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  6. Aude Bonehill
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Editors and Affiliations

  1. Institute for Cancer Research, Dept. Immunology, Norwegian Radium Hospital, Montebello, Oslo, 0310, Norway

    Mouldy Sioud

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Van Nuffel, A.M., Corthals, J., Neyns, B., Heirman, C., Thielemans, K., Bonehill, A. (2010). Immunotherapy of Cancer with Dendritic Cells Loaded with Tumor Antigens and Activated Through mRNA Electroporation. In: Sioud, M. (eds) RNA Therapeutics. Methods in Molecular Biology, vol 629. Humana Press. https://doi.org/10.1007/978-1-60761-657-3_27

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