July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Effect of Anti-Human C5 Antibodies on Ocular Inflammation in Experimental Autoimmune Uveitis in Humanized C5 Mice

Aixu Sun, Henry Chen, Hua Yang, Adrianna Latuszek, Ying Hu, Pamela Krueger, Tammy Huang, Jingtai Cao, Carmelo Romano

Regeneron Pharmaceuticals, Inc. Tarrytown, NY
Author Affiliations & Notes
  • Aixu Sun
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Henry Chen
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Hua Yang
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Adrianna Latuszek
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Ying Hu
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Pamela Krueger
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Tammy Huang
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Jingtai Cao
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Carmelo Romano
    Regeneron Pharmaceuticals INC, Tarrytown, New York, United States
  • Footnotes
    Commercial Relationships   Aixu Sun, Regeneron Pharmaceuticals Inc (E); Henry Chen, Regeneron Pharmaceuticals Inc (E); Hua Yang, Regeneron Pharmaceuticals Inc (E); Adrianna Latuszek, Regeneron Pharmaceuticals Inc (E); Ying Hu, Regeneron Pharmaceuticals Inc (E); Pamela Krueger, Regeneron Pharmaceuticals Inc (E); Tammy Huang, Regeneron Pharmaceuticals Inc (E); Jingtai Cao, Regeneron Pharmaceuticals Inc (E); Carmelo Romano, Regeneron Pharmaceuticals Inc (E)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 2534. doi:
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      Aixu Sun, Henry Chen, Hua Yang, Adrianna Latuszek, Ying Hu, Pamela Krueger, Tammy Huang, Jingtai Cao, Carmelo Romano; Effect of Anti-Human C5 Antibodies on Ocular Inflammation in Experimental Autoimmune Uveitis in Humanized C5 Mice

      Aixu Sun, Henry Chen, Hua Yang, Adrianna Latuszek, Ying Hu, Pamela Krueger, Tammy Huang, Jingtai Cao, Carmelo Romano

      Regeneron Pharmaceuticals, Inc. Tarrytown, NY. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2534.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Complement has been implicated in ocular inflammation. We have shown that ocular inflammation in murine experimental autoimmune uveitis (EAU) is mitigated by inhibiting C5 activity, either by genetic deletion or pharmacologic inhibition with an anti-C5 antibody. The present study evaluates the effect of anti-human C5 antibodies on EAU in humanized C5 mice.

Methods : Humanized C5 mice, in which the human C5 (hC5) gene is substituted for the mouse (exon2-41), were used. EAU was induced as previously described, using pertussis toxin, IRBP and complete Frend’s. Anti-hC5 or isotype control mAb was administered through S.C injections every 3 days from day 5 to 28 post induction. OCT was used to assess levels of inflammation on days -1, 7, 14, 21 and 28. All animals were euthanized on day 28. Eyes and blood samples were harvested. Mouse anti-human(MAHA) and C5 Ab concentration were measured in the serum. Eye tissues were used for flow cytometry analysis. Data was analyzed by ANOVA.

Results : Systemic administration of 10mg/kg of anti-hC5 significantly reduced OCT score, retina thickness and vitreous cell cluster count compared with control Ab or no treatment at week 2 and 3 (p<0.01), and no treatment at week 4 (p<0.001). Only one mouse developed a high MAHA titer in the 10mg/kg dosed group. Systemic administration of 10mg/kg of a different anti-hC5 mAb also significantly reduced OCT score, retina thickness and vitreous cell cluster count in EAU mice. This was evident by flow cytometry which demonstrated less ocular immune cell (macrophage and dendritic cells) infiltration.

Conclusions : These results show that anti-hC5 mAbs reduce EAU disease in humanized C5 mice. C5 is a potential therapeutic target for autoimmune uveitis.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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