1274 - Development of a Novel Recombinant Biotherapeutic with Applications in Targeted Therapy of Human Arthritis

Monday, November 7, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Panagiotis Kamperidis1, Tahereh Kamalati1, Mathieu Ferrari1, Lewis Lee1, Rita Jones1, Toby Garrood1, Malcolm D. Smith2, Soraya Diez-Posada1, Chris Hughes1, Ciara Finucane1, Stephen Mather1, Ahuva Nissim1, Andrew J. T. George1 and Costantino Pitzalis3, 1London, United Kingdom, 2Adelaide, Australia, 3Centre for Experimental Medicine and Rheumatology, QMUL, London, United Kingdom
Presentation Number: 1274

Background/Purpose: 

To isolate recombinant antibodies with specificity for human arthritic synovium and to develop targeting reagents with joint specific delivery capacity for therapeutics and/or diagnostic applications.

Method:

In vivo single chain antibody (scFv) Phage Display screening using a human synovial xenograft model was used to isolate antibodies specific to the microvasculature of human arthritic synovium.  scFv antibody tissue specific reactivity was assessed by immunostaining of: (i) synovial tissues from normal controls, RA and OA patients,  (ii) normal human tissues arrays and (iii) tissues from other inflammatory diseases displaying neovasculogenesis. In vivo scFv antibody tissue specific targeting capacity was examined in the human synovial xenograft model using both 125I labeled and biotinylated antibody.

Result: 

We have isolated a novel human, recombinant antibody, scFv A7, with specificity for the microvasculature of human arthritic synovium. We show that in vivo, this antibody can efficiently target human synovial microvasculature in SCID mice transplanted with human arthritic synovial xenografts.  Our results demonstrate that scFv A7 antibody has no reactivity with the microvasculature or, other cellular components, found in a comprehensive range of normal human tissues including normal human synovium. Further, we show that the reactivity of the scFv A7 antibody is not a common feature of neovasculagenesis associated with chronic inflammatory conditions.

Conclusion: 

Here we report for the first time the identification of a scFv antibody, A7, that specifically recognizes an epitope expressed in the microvasculature of human arthritic synovium and has the potential to be developed as a joint specific pharmaceutical.


Keywords: antibodies and rheumatoid arthritis (RA)

Disclosure: P. Kamperidis, None; T. Kamalati, None; M. Ferrari, None; L. Lee, None; R. Jones, None; T. Garrood, None; M. D. Smith, None; S. Diez-Posada, None; C. Hughes, None; C. Finucane, None; S. Mather, None; A. Nissim, None; A. J. T. George, None; C. Pitzalis, None.