Peptides having immunomodulatory properties
Inventors
Jaynes, Jesse • Lopez, Henry Wilfred • Martin, George R. • YATES, Clayton • Garvin, Charles
Assignees
Publication Number
US-11147854-B2
Publication Date
2021-10-19
Expiration Date
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Abstract
The present disclosure provides novel peptides that having immunomodulatory activities in vitro and in vivo. The peptides can include a particular striapathic region of alternating hydrophilic and hydrophobic modules that can adopt an amphipathic conformation under physiological conditions. This disclosure provides peptides that can specifically bind to key functional regions on one or more signaling proteins, particularly pro-inflammatory cytokines, macrophage inhibition proteins, and histone regulation proteins. This disclosure includes peptides that are sufficiently stable in the circulation to allow for intravenous administration. Pharmaceutical compositions including the subject peptides are also provided. The subject peptides find use in methods of modulating macrophage activity. In some cases, the peptide is a CD206-binding agent. Also provided are methods of treating a subject for a condition associated with chronic inflammation using the peptides and compositions of this disclosure.
Core Innovation
Novel peptides having immunomodulatory activities in vitro and in vivo are provided. The peptides can include a particular striapathic region of alternating hydrophilic and hydrophobic modules that can adopt an amphipathic conformation under physiological conditions. The peptides can specifically bind to key functional regions on one or more signaling proteins, particularly pro-inflammatory cytokines, macrophage inhibition proteins, and histone regulation proteins, and pharmaceutical compositions including the subject peptides are also provided.
Various agents can cause prolonged and excessive inflammation resulting in chronic inflammation that contributes to many diseases and fibrosis. Therapeutic agents that reduce inflammation without harmful side effects are therefore of great interest. The disclosure provides peptides that are sufficiently stable in the circulation to allow for intravenous administration and that find use in methods of modulating macrophage activity and in methods of treating a subject for a condition associated with chronic inflammation.
Claims Coverage
Two inventive features are identified from the independent claims.
Immunomodulatory peptide comprising selected sequences
An immunomodulatory peptide, comprising: a peptide sequence selected from the group consisting of FAOOFAOOFO (RP850) (SEQ ID NO: 19), FWKRFVRKWR (RP837) (SEQ ID NO: 2) and FWKKFVKKWK (RP841) (SEQ ID NO: 7).
Immunomodulatory peptide consisting of selected sequences
An immunomodulatory peptide, consisting of: a peptide sequence selected from the group consisting of FWKRFVRKWR (RP837) (SEQ ID NO: 2), FWKKFVKKWK (RP841) (SEQ ID NO: 7), and FAOOFAOOFO (RP850) (SEQ ID NO: 19).
The independent claims recite immunomodulatory peptides defined by specific peptide sequences (FAOOFAOOFO; FWKRFVRKWR; FWKKFVKKWK) either as comprising or consisting of those sequences, with dependent claims covering pharmaceutical compositions and methods of treating conditions associated with chronic inflammation including scleroderma and lung fibrosis.
Stated Advantages
Peptides having immunomodulatory activities in vitro and in vivo.
Peptides include a striapathic region of alternating hydrophilic and hydrophobic modules that can adopt an amphipathic conformation under physiological conditions.
Peptides can specifically bind to key functional regions on one or more signaling proteins, particularly pro-inflammatory cytokines, macrophage inhibition proteins, and histone regulation proteins.
Peptides are sufficiently stable in the circulation to allow for intravenous administration.
Peptides find use in methods of modulating macrophage activity and as CD206-binding agents.
Peptides are described as useful in methods of treating subjects for conditions associated with chronic inflammation.
Examples report reduction in tumor volume when peptides are used with a PD-1 checkpoint inhibitor.
Examples report reduction of bleomycin-induced lung fibrosis in a mouse model.
Examples report selective reduction of viability of macrophages from scleroderma patients.
Documented Applications
Methods of modulating macrophage activity, including macrophage polarization, using the subject peptides.
Use as CD206-binding agents to bind CD206, including binding to mannose-binding sites, fibronectin domains, and C-type carbohydrate recognition domains (CRD), and to modulate CD206 activity.
Methods of treating or preventing conditions associated with chronic inflammation, including scleroderma and lung fibrosis, by administering the subject peptides or compositions.
Methods of treating cancer and solid tumors using the subject peptides, alone or in combination with additional agents; cancers explicitly listed include colon, breast, leukemia, lymphoma, ovarian, prostate, liver, lung, testicular, cervical, bladder, endometrial, kidney, melanoma, thyroid, brain, and ophthalmic cancers.
Combination therapies including the subject peptides with chemotherapeutic agents (examples named include Gemcitabine, Docetaxel, Abraxane), immunotherapies, immune checkpoint inhibitors, and vaccination therapies such as Th17-inducing dendritic cell vaccines.
Pharmaceutical compositions and formulations of the subject peptides for routes including oral, parenteral, inhalation, topical, intravenous, subcutaneous, intratumoral, and mucosal administration, and enteric-coated oral forms.
Nanoparticle and liposomal formulations and albumin-containing nanoparticle formulations for protected, sustained, and targeted delivery of the peptides.
Kits comprising an immunomodulatory peptide that is a CD206-binding peptide and an additional agent (e.g., a chemotherapeutic or immunotherapeutic agent) with instructions for administration.
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