Testing of monoclonal antibodies against the T-cell receptor associated with ankylosing spondylitis

Israelson MA1,3, Stepanov AV2, Staroverov DB1,3, Shagina IA1, Misorin AK4, Evstratieva AV4, Merzlyak EM1,3, Bogdanova EA1, Britanova OV3, Lukyanov SA1
About authors

1 Department of Molecular Technologies, Institute of Translational Medicine,
Pirogov Russian National Research Medical University, Moscow

2 Department of Peptide and Protein Technologies, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow

3 Department of Adaptive Immunity Genomics, Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Moscow

4 BIOCAD, Saint-Petersburg

Correspondence should be addressed: Olga V. Britanova
Miklouho-Maclay 16/10, Moscow, 117997; moc.liamg@natirblo

About paper

Funding: this work was supported by the Ministry of Science and Education of the Russian Federation, Project ID RFMEFI60716X0158.

Received: 2018-09-13 Accepted: 2018-10-11 Published online: 2018-12-04

In the last decade there has been a tendency to move away from the symptomatic treatment and embrace targeted therapies. This process is underpinned by the accumulated knowledge of the mechanisms underlying the pathogenesis of diseases and driven by the advances in biotechnologies. T-cell receptors with variable TRBV9 β-chain regions have been recently associated with spondyloarthritis including its subtype, ankylosing spondylitis. The aim of this work was to engineer a chimeric monoclonal antibody targeting the variable region of the T-cell receptor β-chain encoded by the TRBV9 gene segment and assess its specificity and cytotoxicity. Using flow cytometry and next generation sequencing, we demonstrate that the engineered chimeric antibody is highly specific and exhibits cytotoxic activity against its target. Approaches based on the use of therapeutic chimeric antibodies against pathogenic T-clones may hold great promise for the therapy of autoimmune disorders in general and AS in particular.

Keywords: autoimmune disease, ankylosing spondylitis, therapeutic antibody for autoimmunity treatment, T-cell receptor