2006 Fiscal Year Final Research Report Summary
New therapeutic strategies : a chimeric fusion protein inhibits allergic reactivity
| Project/Area Number |
17591809
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Osaka Medical College |
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Principal Investigator |
TERADA Tetsuya Osaka Medical College, Faculty of Medicine, Research assistant, 医学部, 助手 (60343670)
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| Co-Investigator(Kenkyū-buntansha) |
KAWATA Ryo Osaka Medical College, Faculty of Medicine, Assistant Professor, 医学部, 助教授 (40224787)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Rodent / Fc Receptors / Allergy / Immunotherapy / asthma / chimeric protein / 気道過敏性 |
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| Research Abstract |
We have undertaken to develop new therapies for allergic diseases by taking advantage of negative signaling via immunoreceptor tyrosine-based inhibition motif (ITIM)-containing receptors. We constructed bi-functional molecules that indirectly crosslink Fcε receptors to the FcγII receptors on targeted cells.
This approach employed co-aggregation of FcεRI and FcγRII using an antigen-specific chimeric fusion protein (GFD) that was composed of the human Fcγ and the major cat allergen, Fel d1. GFD was designed to block mediator release by directly attaching to Fcγ receptors and at the same time indirectly binding to FcεRI via Fel d1 antigen specific IgE already bound to FcεRIs. GFD was expected to function as a safer form of antigen specific form of immunotherapy with GFD blocking acute reactivity to cat, e.g. not functioning as an allergen while still functioning as an immunogen.
GFD inhibited PCA reactivity to Fel d1 in transgenic mice but did not induce skin reactivity itself at sensitized sites. Balb/c mice sensitized to Fel dl and challenged intratracheally (IT) on day 28 and 42, showed a fall in temperature and increased lung resistance, indicating systemic and pulmonary allergic reactions. Mice given of 5 μg GFD subcutaneously on days 7, 14 and 21 showed inhibition of systemic reactivity to IT challenge at days 28 and 42. GFD inhibited Fel d1-induced allergic response in mice.
This chimeric gamma-allergen protein platform may provide allergen-specific therapy with safety profile that may be critical in situations such as food allergy.
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