Dendritic Cell mRNA Vaccines
Dendritic cells take up and process antigens and present them to T cells. Therefore, DC has been well studied as a means of stimulating cancer-specific T cell responses. An effective strategy for programming DCs is to use mRNA, and the vaccine consisting of mRNA-modified DCs has shown promising results in clinical trials. Equipped with a team of professional scientists, Creative Biolabs is capable of providing specialized support in the design, production and evaluation of mRNA-based dendritic cell vaccines to bring your mRNA therapeutics closer to clinical realization. We can accommodate the specific attributes of your project and provide flexible and integrated solutions.
A method that is widely used to load DCs with antigenic information is the use of peptides. However, this approach has several disadvantages, 1) Prior identification of peptides; 2) HLA restriction of the patients; 3) Short half-life peptide/HLA complex which limits the duration of antigen presentation. mRNA is a versatile tool to program dendritic cells as it is a polyvalent molecule with an attractive safety profile, inducing transient but sufficiently long and high protein expression without the risk of integrating into the host genome. The strategy of using mRNA to deliver the anti-tumor message has gained a lot of attention in recent years. DCs can be modified with mRNA using ex vivo or an in situ methods. Disadvantages of peptide-loaded dendritic cells that can be circumvented by mRNA loading.
- Undefined epitopes can be presented
- Multiple epitopes of 1 antigen
- No HLA restriction of the patients
- Extended antigen presentation
- The possibility of modifying mRNA sequence
mRNA-based Dendritic Cell Vaccines
The interest in using mRNA as a means of loading tumor antigens onto DCs began to rise in the late 1990s. mRNA-based DC vaccines rely on the ability of DCs to uptake mRNA, translate it to protein, and then process it into peptides and present them to CD8+ T cells. DC phagocytose mRNA through giant cell drinking, a process that rapidly decreases after DC activation. Since the mRNA itself can activate pattern recognition receptors (TLR3 and TLR7, etc.), and thus induce DC activation, the process is self-limiting. Additionally, mRNA has to move through the endosome, which carries the risk that only a small portion of the mRNA will reach the cytoplasm, where the cytoplasm is converted to protein.
mRNA has proven to be an excellent tool for modifying DCs by antigen loading and delivery of functional message, stimulating or inhibiting its stimulatory potential. With the commitment of being your best vaccine development partner, Creative Biolabs has established the utmost efficient integrated solutions to innovate and accelerate your vaccine development for cancer. If you are interested in our services, please contact us to get more information or directly send us an online inquiry.
Reference
- Benteyn D, et al. mRNA-based dendritic cell vaccines. Expert Rev Vaccines. 2015, 14(2):161-76.
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