June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
The high affinity IgE receptor-IgG1 Fc fusion protein (mKS) shows effectiveness against allergic conjunctivitis
Author Affiliations & Notes
  • Akihiro Misawa
    Research Division, Kissei Pharmaceutical Co., Ltd., Azumino, Japan
  • Shunya Awaka
    Research Division, Kissei Pharmaceutical Co., Ltd., Azumino, Japan
  • Kumi Tsuchioka
    Research Division, Kissei Pharmaceutical Co., Ltd., Azumino, Japan
  • Shota Yamamoto
    Research Division, Kissei Pharmaceutical Co., Ltd., Azumino, Japan
  • Itaru Maruyama
    Research Division, Kissei Pharmaceutical Co., Ltd., Azumino, Japan
  • Yoichi Inada
    Research Division, Kissei Pharmaceutical Co., Ltd., Azumino, Japan
  • Satoshi Tatemichi
    Research Division, Kissei Pharmaceutical Co., Ltd., Azumino, Japan
  • Hiroo Takeda
    Research Division, Kissei Pharmaceutical Co., Ltd., Azumino, Japan
  • Footnotes
    Commercial Relationships   Akihiro Misawa, Kissei Pharmaceutical Co., Ltd. (E); Shunya Awaka, Kissei Pharmaceutical Co., Ltd. (E); Kumi Tsuchioka, Kissei Pharmaceutical Co., Ltd. (E); Shota Yamamoto, Kissei Pharmaceutical Co., Ltd. (E); Itaru Maruyama, Kissei Pharmaceutical Co., Ltd. (E); Yoichi Inada, Kissei Pharmaceutical Co., Ltd. (E); Satoshi Tatemichi, Kissei Pharmaceutical Co., Ltd. (E); Hiroo Takeda, Kissei Pharmaceutical Co., Ltd. (E)
  • Footnotes
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Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2943. doi:
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      Akihiro Misawa, Shunya Awaka, Kumi Tsuchioka, Shota Yamamoto, Itaru Maruyama, Yoichi Inada, Satoshi Tatemichi, Hiroo Takeda; The high affinity IgE receptor-IgG1 Fc fusion protein (mKS) shows effectiveness against allergic conjunctivitis. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2943.

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

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Abstract

Purpose : Inhibition of IgE, a major factor in allergic reactions, is important for the treatment of allergic diseases, and anti-IgE antibodies such as omalizumab are recognized as being useful therapies for allergic diseases. Since it is also known that the IgE level in tears is increased in patients with allergic conjunctivitis, a topical treatment containing anti-IgE antibody is expected to be effective. However, few reports have evaluated the efficacy of anti-IgE therapy administered locally. The purpose of this study was to investigate the effect of our high affinity IgE receptor-IgG1 Fc fusion protein (mKS) as an eye drop on allergic conjunctivitis.

Methods : 1) Mechanism of action: The neutralizing activities of mKS against human and mouse IgE using competitive ELISA were examined. The impact of mKS on IgE receptor density expressed on mouse bone marrow derived mast cells (BMMC) using flow cytometry was investigated. 2) Pharmacological effects using an animal model: The efficacies of mKS qd, epinastine hydrochloride ophthalmic solution 0.05% qid and olopatadine hydrochloride ophthalmic solution 0.1% qid on conjunctival vascular permeability in a Ragweed-induced mouse allergic conjunctivitis model were evaluated. Measurement days were the last day of 2-week repeated instillations and 7 days after the final instillation.

Results : The neutralizing activities of mKS against human and mouse IgE were 0.130 ± 0.009 nmol/L and 0.213 ± 0.032 nmol/L, respectively. IgE receptor density expressed on BMMC was increased IgE dose (0.1 to 1 μg/mL) and exposure time (24 or 48hr) dependently. The increase in IgE receptor density was significantly suppressed by mKS (0.1 to 5 nmol/L) administered simultaneously with IgE. On the final day of repeated instillations for 2 weeks in the animal model, mKS significantly suppressed the increase of conjunctival vascular permeability, as much as the other agents. At 7 days after the final instillation, only mKS sustained this suppression whereas the effects of other agents showed attenuation.

Conclusions : Our high affinity IgE receptor-IgG1 Fc fusion protein, mKS, neutralized IgE and suppressed the increase in IgE receptor density on mast cells. This topical mKS treatment (eye drops) showed a unique efficacy differing from that of typical ophthalmic drugs. These results suggested mKS eye drops to potentially be useful for treating allergic conjunctivitis.

This is a 2020 ARVO Annual Meeting abstract.

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