Humanized SCID mice models of SLE

Nikola Kerekov, Nikolina Mihaylova, J. Prechl, Andrey Tchorbanov

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

The pathological DNA-specific B cells in Systemic lupus erythematosus are a logical target for a selected therapeutic intervention. It has been recently shown that complement receptor type 1 on human B and T-lymphocytes has suppressive activity. The cocrosslinking of this receptor with the B-cell receptor (BCR) inhibits B cell activation and proliferation and it could be an attractive new target for negative signal delivery. Experimental therapy in humans is limited by many restrictions. Severe combined immunodeficiency (SCID) mice, which lack both T and B lymphocytes and accept xenogenic cells have been used for human cell transfer for evaluating the pathogenesis of human SLE. We hypothesize that it may be possible to re-establish tolerance to native DNA in humanized SCID mice with cells transferred from SLE patients by administering to them a chimeric molecule, containing a monoclonal antibody against human inhibitory complement receptor type 1 coupled to a decapeptide DWEYSVWLSN that mimics DNA antigenically. These protein-engineered molecules are able to cocrosslink selectively the antigen receptors of B-cells possessing anti-native DNA specificity with the inhibitory surface receptors, thus delivering a strong suppressive signal.

Original languageEnglish
Pages (from-to)1261-1266
Number of pages6
JournalCurrent Pharmaceutical Design
Volume17
Issue number13
Publication statusPublished - May 2011

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Severe Combined Immunodeficiency
B-Lymphocytes
Complement Receptors
DNA
T-Lymphocytes
B-Cell Antigen Receptors
Investigational Therapies
Systemic Lupus Erythematosus
Monoclonal Antibodies
Cell Proliferation
Proteins

Keywords

  • Chimeric molecules
  • Inhibitory B cell receptors
  • SCID models of SLE

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

Kerekov, N., Mihaylova, N., Prechl, J., & Tchorbanov, A. (2011). Humanized SCID mice models of SLE. Current Pharmaceutical Design, 17(13), 1261-1266.

Humanized SCID mice models of SLE. / Kerekov, Nikola; Mihaylova, Nikolina; Prechl, J.; Tchorbanov, Andrey.

In: Current Pharmaceutical Design, Vol. 17, No. 13, 05.2011, p. 1261-1266.

Research output: Contribution to journalArticle

Kerekov, N, Mihaylova, N, Prechl, J & Tchorbanov, A 2011, 'Humanized SCID mice models of SLE', Current Pharmaceutical Design, vol. 17, no. 13, pp. 1261-1266.
Kerekov N, Mihaylova N, Prechl J, Tchorbanov A. Humanized SCID mice models of SLE. Current Pharmaceutical Design. 2011 May;17(13):1261-1266.
Kerekov, Nikola ; Mihaylova, Nikolina ; Prechl, J. ; Tchorbanov, Andrey. / Humanized SCID mice models of SLE. In: Current Pharmaceutical Design. 2011 ; Vol. 17, No. 13. pp. 1261-1266.
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