HMGN polypeptides as immune enhancers and HMGN antagonists as immune suppressants
Inventors
Yang, De • Oppenheim, Joost J. • Bustin, Michael
Assignees
US Department of Health and Human Services
Publication Number
US-9567566-B2
Publication Date
2017-02-14
Expiration Date
2029-07-24
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Abstract
A method of enhancing an antigen-specific immune response in a host comprising administering to the host an HMGN polypeptide comprising at least one of HMGN1, HMGN3a, HMGN3b, HMGN4, Nsbp1, or a functional fragment thereof, in an amount effective to enhance an antigen-specific immune response; as well as a pharmaceutical composition comprising an HMGN polypeptide comprising at least one of HMGN1, HMGN3a, HMGN3b, HMGN4, Nsbp1, or a functional fragment thereof, and an antigen, or nucleic acids encoding such molecules; and related methods and compositions.
Core Innovation
The invention provides methods and compositions for enhancing an antigen-specific immune response in a host by administering an HMGN polypeptide selected from HMGN1, HMGN3a, HMGN3b, HMGN4, Nsbp1, or functional fragments thereof. The methods involve enhancing activation or recruitment of dendritic cells and shifting the Th-1/Th-2 immune response balance towards a Th-1 type. Pharmaceutical compositions comprising HMGN polypeptides and antigens are also described, including nucleic acids encoding these molecules.
The problem addressed by the invention arises from diminished or unfavorably shifted immune responses in patients due to disease or treatments, such as in cancer patients. Specifically, an immune response may be suppressed or shifted away from a Th-1 pro-inflammatory type towards a Th-2 anti-inflammatory type, resulting in more rapid disease progression and reduced treatment effectiveness. Conversely, heightened Th-1 responses also can be disadvantageous in other diseases. Therefore, methods to modulate immune responses to restore or enhance the desired balance are needed.
Claims Coverage
The patent includes three independent claims covering methods to enhance immune response, dendritic cell activation or recruitment, and shift the Th-1/Th-2 balance using a polypeptide comprising Nsbp1.
Enhancement of antigen-specific immune response
A method comprising administering an antigen and a polypeptide comprising Nsbp1 (SEQ ID NO: 5) to a host in an amount effective to enhance an antigen-specific immune response.
Enhancement of dendritic cell activation or recruitment
A method comprising administering an antigen and a polypeptide comprising Nsbp1 (SEQ ID NO: 5) to a host in an amount effective to enhance activation and recruitment of dendritic cells.
Shifting the Th-1/Th-2 immune response balance
A method comprising administering an antigen or nucleic acid encoding the antigen and a polypeptide comprising Nsbp1 (SEQ ID NO: 5) in an amount effective to shift the Th-1/Th-2 immune response balance towards a Th-1 type immune response.
The independent claims cover methods of using Nsbp1 polypeptides to enhance antigen-specific immune responses, stimulate dendritic cell activation and recruitment, and shift immune responses towards a Th-1 type, often in combination with antigens or nucleic acids encoding such antigens.
Stated Advantages
HMGN polypeptides enhance antigen-specific immune responses quantitatively and qualitatively by shifting the Th-1/Th-2 balance towards Th-1.
Activation and recruitment of dendritic cells is enhanced by HMGN polypeptides, promoting immune response effectiveness.
Use of endogenous HMGN polypeptides is believed to avoid toxic effects in mammals.
Documented Applications
Treatment or prevention of diseases, especially cancer, using methods or compositions comprising HMGN polypeptides and tumor antigens.
Enhancement of immune responses to microbial antigens, including bacterial and viral pathogens.
Suppression of immune responses using HMGN polypeptide antagonists to treat diseases associated with heightened Th-1 type immune responses such as parasitic infections and autoimmune or inflammatory disorders.
Use in vaccination protocols, such as enhancing responses to anthrax vaccine or ovalbumin antigen.
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