Dr David Escors

In our group we study the cellular and molecular mechanisms of antigen recognition. More specifically, the role of antigen presentation by dendritic cells to antigen-specific T lymphocytes in immune regulation . The results obtained from our results are applied for the development of vaccines to treat autoimmune disorders such as rheumatoid arthritis, and cancer. Read more below..

Dr David Escors (right), Dr Frederick Arce (centre) and Dr Akira Shimizu (left)

Dr David Escors (right), Dr Frederick Arce (centre) and Dr Akira Shimizu (left)

Our Research

In our group we study the cellular and molecular mechanisms of antigen recognition. More specifically, the role of antigen presentation by dendritic cells (DCs) to antigen-specific T lymphocytes in immune regulation (2, 6). The results obtained from our results are applied for the development of vaccines to treat autoimmune disorders such as rheumatoid arthritis, and cancer (1, 3, 5, 6).

Dendritic cells are probably the most immunogenic professional antigen presenting cells. Interestingly, they do not only trigger immune responses, but they also establish antigen-specific tolerance. The main mechanism by which DCs regulate T cell functions is at the level of antigen presentation, in the immunological synapse. T recognise antigens associated to major histocompatibility complex molecules (MHC) on the surface of DCs through binding of their specific TCRs. However, this recognition is not sufficient, and for full T cell activation, binding of particular ligand molecules on the APC surface with corresponding receptors on the T cell surface (co-stimulation) has to occur. The integration of positive and negative signals during co-stimulation provides a checkpoint at which T cell responses can be modulated.

Using gene therapy techniques based on lentiviral vectors (4, 7, 8), we modify DC functions ex vivo and in vivo by (i) expression of constitutive activators/inhibitors of intracellular signalling pathways (1, 5), or (ii) by silencing of specific co-stimulatory molecules using lentivirus-based short-hairpin delivery systems (1).

So far, we have demonstrated that specific activation of MAPK p38 and JNK1 and inhibition of ERK increase the capacity of DCs to induce effective immunity and anti-tumour activities (2, 5). We have also shown that targeted ERK activation in DCs differentiates tolerogenic DCs and expands antigen-specific regulatory T cells (1).

This approach is effective for the treatment of inflammatory arthritis in mouse models. We have demonstrated that it is particularly effective in human DCs, and we are translating ERK activation into a clinically relevant protocol in human patients of rheumatoid arthritis.

References

1. Arce, F., K. Breckpot, H. Stephenson, K. Karwacz, M. R. Ehrenstein, M. Collins, and D. Escors. 2011. Selective ERK activation differentiates mouse and human tolerogenic dendritic cells, expands antigen-specific regulatory T cells, and suppresses experimental inflammatory arthritis. Arthritis Rheum 63:84-95.

2. Breckpot, K., and D. Escors. 2009. Dendritic Cells for Active Anti-cancer Immunotherapy: Targeting Activation Pathways Through Genetic Modification. Endocr Metab Immune Disord Drug Targets 9:328-343.

3. Breckpot, K., D. Escors, F. Arce, L. Lopes, K. Karwacz, S. Van Lint, M. Keyaerts, and M. Collins. 2010. HIV-1 lentiviral vector immunogenicity is mediated by Toll-like receptor 3 (TLR3) and TLR7. J. Virol. 84:5627-5636.

4. Escors, D., and K. Breckpot. 2010. Lentiviral Vectors in Gene Therapy: Their Current Status and Future Potential. Arch Immunol Ther Exp 58:107-119.

5. Escors, D., L. Lopes, R. Lin, J. Hiscott, S. Akira, R. J. Davis, and M. K. Collins. 2008. Targeting dendritic cell signalling to regulate the response to immunisation. Blood 111:3050-61.

6. Goold, H. D., D. Escors, T. J. Conlan, R. Chakraverty, and C. L. Bennett. 2011. Conventional DC are required for the activation of helper-dependent CD8 T cell responses after cutaneous vaccination with lentiviral vectors J. Immunol. doi:10.4049/jimmunol.1002529.

7. Perro, M., J. Tsang, S. A. Xue, D. Escors, M. Cesco-Gaspere, C. Pospori, L. Gao, D. Hart, M. Collins, H. Stauss, and E. C. Morris. 2010. Generation of multi-functional antigen-specific human T-cells by lentiviral TCR gene transfer. Gene Ther.

8. Perro, M., S. A. Xue, J. Tsang, M. Cesco-Gaspere, D. Escors, M. Collins, E. Morris, and H. Stauss. 2008. Lentiviral TCR gene transfer for adoptive immunotherapy of cancer. EJC supplements 6:163-164.

Publications

1. Arce, F., K. Breckpot, H. Stephenson, K. Karwacz, M. R. Ehrenstein, M. Collins, and D. Escors. 2011. Selective ERK activation differentiates mouse and human tolerogenic dendritic cells, expands antigen-specific regulatory T cells, and suppresses experimental inflammatory arthritis. Arthritis Rheum 63:84-95.

2. Breckpot, K., and D. Escors. 2009. Dendritic Cells for Active Anti-cancer Immunotherapy: Targeting Activation Pathways Through Genetic Modification. Endocr Metab Immune Disord Drug Targets 9:328-343.

3. Breckpot, K., D. Escors, F. Arce, L. Lopes, K. Karwacz, S. Van Lint, M. Keyaerts, and M. Collins. 2010. HIV-1 lentiviral vector immunogenicity is mediated by Toll-like receptor 3 (TLR3) and TLR7. J. Virol. 84:5627-5636.

4. Escors, D., and K. Breckpot. 2010. Lentiviral Vectors in Gene Therapy: Their Current Status and Future Potential. Arch Immunol Ther Exp 58:107-119.

5. Escors, D., L. Lopes, R. Lin, J. Hiscott, S. Akira, R. J. Davis, and M. K. Collins. 2008. Targeting dendritic cell signalling to regulate the response to immunisation. Blood 111:3050-61.

6. Goold, H. D., D. Escors, T. J. Conlan, R. Chakraverty, and C. L. Bennett. 2011. Conventional DC are required for the activation of helper-dependent CD8 T cell responses after cutaneous vaccination with lentiviral vectors J. Immunol. doi:10.4049/jimmunol.1002529.

7. Perro, M., J. Tsang, S. A. Xue, D. Escors, M. Cesco-Gaspere, C. Pospori, L. Gao, D. Hart, M. Collins, H. Stauss, and E. C. Morris. 2010. Generation of multi-functional antigen-specific human T-cells by lentiviral TCR gene transfer. Gene Ther.

8. Perro, M., S. A. Xue, J. Tsang, M. Cesco-Gaspere, D. Escors, M. Collins, E. Morris, and H. Stauss. 2008. Lentiviral TCR gene transfer for adoptive immunotherapy of cancer. EJC supplements 6:163-164.

Research Collaborators

Our main collaborators are:

Within UCL: Mary Collins, Michael Ehrenstein, Arne Akbar, Clare Bennett and Mona Bajaj-Elliot (ICH).

Outside UCL:
University of Brussels: Karine Breckpot and Kris Thielemans

Contact details

Currently: Windeyer Building, 46 Cleveland Street
Telephone: 020-7679-9348
Email: d.escors [at] ucl.ac.uk 

From May 2011: Rayne Building, 5 University Street, LONDON WC1E 6JF

Email: d.escors [at] ucl.ac.uk 

Page last modified on 04 apr 11 12:04 by Karen Rumsey