**Author details**

Winni De Haes *Institute of Tropical Medicine of Antwerp, Department of Biomedical Sciences, Virology Unit, Antwerp, Belgium* 

Charlotte Pollard *Institute of Tropical Medicine of Antwerp, Department of Biomedical Sciences, Virology Unit, Antwerp, Belgium Laboratory of Molecular Immunology, Ghent University, Belgium* 

Guido Vanham *Institute of Tropical Medicine of Antwerp, Department of Biomedical Sciences, Virology Unit, Antwerp, Belgium Faculty of Pharmaceutical, Veterinary and Biomedical Sciences, University of Antwerp, Belgium Faculty of Medicine and Pharmacology, Vrije Universiteit Brussel, Belgium* 

Joanna Rejman *Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Belgium* 

### **Acknowledgement**

54 Immunodeficiency

stimulate HIV-specific T cell responses [311].

in the absence of additional HAART therapy.

**Author details** 

Winni De Haes

*Antwerp, Belgium* 

Charlotte Pollard

*Antwerp, Belgium* 

Guido Vanham

*Antwerp, Belgium* 

Joanna Rejman

**7. Concluding remarks** 

Another possibility to improve immunogenicity is the addition of co-stimulatory molecules. The addition of CD40L to DCs loaded with liposome-complexed HIV-1 proteins could prime HIV-1 specific CD8+ T cells *in vitro* [162]. Within the scope of mRNA transfection, mRNA encoding co-stimulatory molecules can be co-transfected with mRNA encoding an antigen, which has been shown to strongly enhance the capacity of electroporated DCs to

*Ex vivo* loading of DCs shows promising results as an immunotherapy for HIV and cancer. However, the currently applied strategy is not applicable on a large scale, especially in Africa where the largest incidence of HIV infections is observed. The use of particulate vehicles able to directly deliver the antigen of interest, be it proteins, peptides or nucleic acids, into DCs *in vivo* is a very attractive concept. Different antigen formulations can be further tailored with targeting antibodies or immunomodulatory ligands to promote uptake by DCs and to trigger the desired type of immune response. In the context of HIV immunotherapy a large number of epitopes needs to cover a broad panel of quasi species. Therefore, mRNA-based vaccination strategies present an attractive option. In contrast to pDNA, mRNA needs to be delivered only into the cytoplasm and induces transient antigen expression without the risk of genomic insertion. Further research will be required for designing an optimal carrier system preferably comprising an adjuvant, necessary to achieve strong HIV-specific CTL responses with the ultimate goal to control viral replication

*Institute of Tropical Medicine of Antwerp, Department of Biomedical Sciences, Virology Unit,* 

*Institute of Tropical Medicine of Antwerp, Department of Biomedical Sciences, Virology Unit,* 

*Institute of Tropical Medicine of Antwerp, Department of Biomedical Sciences, Virology Unit,* 

*Faculty of Pharmaceutical, Veterinary and Biomedical Sciences, University of Antwerp, Belgium* 

*Laboratory of General Biochemistry and Physical Pharmacy, Ghent University, Belgium* 

*Laboratory of Molecular Immunology, Ghent University, Belgium* 

*Faculty of Medicine and Pharmacology, Vrije Universiteit Brussel, Belgium* 

This work was supported by grants from IUAP (Inter-University Attraction Poles, P6/41 of the Belgian government), FWO (Fund for Scientific Research Flanders, project number G.0226.10) and SOFI-B (Secondary Research Funding ITM). W. De Haes is a doctoral fellow of the Institute for Science and Technology (IWT), Flanders. There is no conflict of interest.

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**Chapter 3** 

© 2012 Lazarova et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Is Anticancer Vaccine Possible:** 

**Experimental Application of Produced mRNA** 

The dendritic cells (DCs) are the most powerful antigen-presenting cells (APC) specialized to induce and regulate immune responses (1,2). The clinical use as cellular adjuvants in vaccination strategies has been aided by the development of methodologies to generate large production of these cells in culture. DCs can be grown ex-vivo from blood monocytes (3,4,5) or enriched CD34+ progenitors (6,7), using combinations of several cytokines/growth factors. Since our laboratory in Oslo routinely uses enriched CD34+ stem cells as stem cell support following high dose radio- and chemotherapy, it was of interest to test if such cells also could be applied for vaccine purposes (8,9), with a long term strategy of combining the

There are some publications indicating that CD34+ derived DC may work more efficiently as APC than those derived from monocytes (10), and recent data confirm that vaccine

Since DCs are able to take up and process serum–derived antigens that are present in the cell cultures, such DC can when injected create unwanted reactions in the patients, in particular when fetal calf serum (FCS) is used. Thus, serum-free culturing condition is preferable, but in most previous culture experiments these conditions resulted in a lower yield of DCs (13,14).

Recently we reported a protocol for producing DCs from monocytes by use of gaspermeable Teflon bags and serum-free medium (15). We have used in the present study this

and reproduction in any medium, provided the original work is properly cited.

programs using CD34+ cell derived DCs lead to improved clinical results (11).

However, most in vitro culture systems for production of DCs include serum (9,11,12).

**Transfected Dendritic Cells Derived from** 

**Enriched CD34+ Blood Progenitor Cells** 

Paula Lazarova, Gunnar Kvalheim and Krassimir Metodiev

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/51544

**1. Introduction** 

two forms of therapy.

