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Lingjun Zhang, Wen Qiu, Brent A Bell, Li Yan, Timothy S Kern, Rachel R Caspi, Feng Lin; Development of mouse anti-mouse CD6 monoclonal antibodies (mAbs) for treating experimental autoimmune uveitis in mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1235.
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© ARVO (1962-2015); The Authors (2016-present)
CD6 is emerging as a promising target for treating T-cell-mediated autoimmune diseases, but whether it could be targeted for treating autoimmune uveitis remains unknown. Disease models developed in mice are widely used to evaluate the potentials of new therapies; however, all existing anti-mouse CD6 mAbs were developed in rats or other animals. These mAbs are highly immunogenic in mice, making long-term and/or multiple treatment studies difficult. We aimed to develop mouse anti-mouse CD6 mAbs and to test their efficacy in treating experimental autoimmune uveitis (EAU).
CD6 knockout (KO) mice were immunized with a recombinant mouse CD6 protein to develop mAb-producing hybridomas. Mouse anti-mouse CD6 mAbs produced by these hybridomas were screened by ELISA, flow cytometry and in vitro T-cell inhibition assays. Finally, one of the identified mouse anti-mouse CD6 mAbs was prepared and tested for its efficacy in halting the development of uveitis induced by already primed uveitogenic T cells in a model of adoptively transferred EAU. Indirect ophthalmoscopy, scanning laser ophthalmoscopy and spectral-domain optical coherence tomography were used to evaluate uveitis severity.
28 positive mouse anti-mouse CD6 mAbs were identified by ELISA: 7 of the 28 were positive in flow cytometry assays; 3 of those 7 inhibited antigen-specific T-cell responses in vitro; 1 of the final 3 functional mAbs that showed a cross-reaction with human CD6 was tested in treatment studies in vivo. This mAb significantly reduced the severity of uveitis, as assessed by the ocular imaging techniques described above.
Mouse anti-mouse CD6 mAbs have been developed, and one of these mAbs is highly effective in treating EAU induced by already activated uveitogenic T cells, suggesting that (a) targeting CD6 would be a new approach for treating autoimmune uveitis and (b) this mouse anti-mouse/human CD6 mAb might be further developed as a new therapeutic for clinical use.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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