Histamine-releasing factor (HRF), HRF-receptor and methods of modulating inflammation
Inventors
Kawakami, Toshiaki • Kawakami, Yuko
Assignees
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Publication Number
US-10370438-B2
Publication Date
2019-08-06
Expiration Date
Abstract
Methods of treating a food allergy, allergic reactions, hypersensitivity, inflammatory responses, inflammation are provided. In one method, histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) is contacted with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin in order to treat the food allergy, allergic reaction, hypersensitivity, inflammatory response, or inflammation. Methods of reducing or decreasing the probability, severity, frequency, duration or preventing a subject from having an acute or chronic food allergy, allergic reaction, hypersensitivity, an inflammatory response or inflammation, are also provided. In one method, histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) is contacted with a compound that inhibits or reduces binding of HRF/TCTP to an immunoglobulin in order to reduce or decrease the probability, severity, frequency, duration or prevent a subject from having an acute or chronic food allergy, allergic reaction, hypersensitivity, an inflammatory response or inflammation.
Core Innovation
The disclosed invention relates to histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) in Ig-mediated allergic and inflammatory disease. HRF/TCTP contributes to allergic and inflammatory responses by binding immunoglobulins, including IgE, and by engaging Fc receptors. HRF/TCTP interaction with the HRF/TCTP receptor is positioned as a key mechanism for allergic reactions, hypersensitivity, and inflammation.
The disclosed invention provides methods of treating allergic reaction, hypersensitivity, an inflammatory response, or inflammation by contacting or administering compounds that inhibit or reduce HRF/TCTP binding to immunoglobulins. The compounds include peptide inhibitors and antibodies that target HRF regions. In particular, inhibitor subsequences or peptides derived from HRF/TCTP are identified for use as inhibitors of HRF/TCTP receptor interaction and HRF/Ig binding.
The disclosure further associates HRF with acute and late anaphylactic cutaneous reactions and with amplification of HRF-driven airway inflammation. It describes reduced probability, severity, frequency, and duration of adverse symptoms in allergy-related settings, including food allergy, and reports prevention of diarrhea in an OVA-induced food allergy model when using GST-N19 (N19 peptide). It also describes a human patient association via HRF-reactive IgG.
Claims Coverage
The document includes one independent claim directed to treating allergic reaction, hypersensitivity, inflammatory response, or inflammation using a peptide inhibitor that targets HRF/TCTP receptor interaction. The dependent claims refine the interaction partner, functional effect, and selected allergic and respiratory conditions.
Peptide inhibitor targeting HRF/TCTP receptor interaction
administering to the subject a peptide inhibitor of histamine releasing factor (HRF)/translationally controlled tumor protein (TCTP) receptor interaction
Peptide sequence limited to HRF/TCTP subsequences of SEQ ID NO:3
said peptide inhibitor consisting of amino acids 1-19 or amino acids 79-142 of SEQ ID NO:3
Treatment of allergic reaction, hypersensitivity, and inflammation
thereby treating the allergic reaction, hypersensitivity, inflammatory response or inflammation
Peptide inhibitor binds to an immunoglobulin
The peptide inhibitor binds to an immunoglobulin
Decreasing probability, severity, frequency, or duration of adverse symptoms
decrease, reduce, inhibit, suppress, limit, control or improve the probability, severity, frequency, or duration of adverse symptoms
Selected allergic reaction types
The allergic reaction is selected from Extrinsic or intrinsic bronchial asthma; Allergic rhinitis; Onchocercal dermatitis; Atopic dermatitis; eczema; rash; allergic urticaria (e.g. hives); allergic conjunctivitis; Drug reactions; Nodules, eosinophilia, rheumatism, dermatitis, and swelling (NERDS); esophageal and a gastrointestinal allergy
Selected respiratory disease or disorder
The respiratory disease or disorder comprises asthma, allergic asthma, bronchiolitis or pleuritis
Overall, the claim set centers on administering a peptide inhibitor that consists of amino acids 1-19 or 79-142 of SEQ ID NO:3 to inhibit HRF/TCTP receptor interaction, with refinements specifying immunoglobulin binding and improvements in probability, severity, frequency, or duration of adverse symptoms, including specified allergic reactions and respiratory disorders.
Stated Advantages
Decrease, reduce, inhibit, suppress, limit, control or improve the probability, severity, frequency, or duration of adverse symptoms.
Treat allergic reaction, hypersensitivity, inflammatory response or inflammation.
Documented Applications
Treating food allergy.
Treating allergic reactions and hypersensitivity.
Treating inflammation, including airway inflammation, asthma and allergic asthma, and airway hyper-responsiveness.
Treating late-phase skin reactions and anaphylaxis.
Treating eosinophilic esophagitis (EoE).
Treating respiratory disorders comprising asthma, allergic asthma, bronchiolitis or pleuritis.
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