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-8227417-B2
Publication Date
2012-07-24
Expiration Date
2029-07-24
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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 involving HMGN polypeptides, specifically HMGN1, HMGN3a, HMGN3b, HMGN4, Nsbp1, or functional fragments thereof, to enhance an antigen-specific immune response in a host. This enhancement includes increasing the activation or recruitment of dendritic cells and shifting the Th-1/Th-2 balance of the host's immune response towards a Th-1 type immune response. The invention also discloses pharmaceutical compositions comprising these HMGN polypeptides along with an antigen or nucleic acids encoding these molecules.
The invention further provides methods for suppressing an immune response by administering an antagonist of an HMGN polypeptide to the host in an amount effective to suppress the immune response. The immune response modulation centers around the balance of Th-1 and Th-2 immune types, where enhancing Th-1 responses is beneficial in certain disease contexts like cancer, and suppressing Th-1 responses is advantageous in diseases characterized by detrimental heightened Th-1 immunity such as autoimmune disorders and parasitic infections.
The problem addressed by the invention is the diminished or disadvantageously polarized immune response in patients, which can limit disease treatment effectiveness or contribute to disease progression. Specifically, diseases and treatments may shift immune responses away from the Th-1 pro-inflammatory type to the Th-2 anti-inflammatory type, reducing effectiveness of immune-mediated disease control, as observed in cancer and other disease states. There is a need for methods to modulate immune responses to achieve better therapeutic outcomes.
Claims Coverage
The patent claims include three independent claims directed to methods of enhancing immune responses using HMGN polypeptides together with an antigen in a host.
Method of enhancing an antigen-specific immune response using HMGN polypeptides
Administering to a host an antigen and a polypeptide comprising HMGN1 (SEQ ID NO: 1), with the additional administration of one or more of HMGN3a, HMGN3b, HMGN4, and Nsbp1, in an amount effective to enhance an antigen-specific immune response.
Method of enhancing activation or recruitment of dendritic cells using HMGN polypeptides
Administering to a host an antigen and a polypeptide comprising HMGN1 (SEQ ID NO: 1), and optionally one or more of HMGN3a, HMGN3b, HMGN4, and Nsbp1, in an amount effective to enhance the activation or recruitment of dendritic cells in the host.
Method of shifting Th-1/Th-2 immune balance towards Th-1 using HMGN polypeptides
Administering to a host an antigen and a polypeptide comprising HMGN1 (SEQ ID NO: 1), together with optionally one or more of HMGN3a, HMGN3b, HMGN4, and Nsbp1, in an amount effective to shift the immune response balance towards a Th-1 type immune response.
The independent claims cover methods of using HMGN polypeptides alone or in combination with multiple antigens to enhance antigen-specific immune responses, activate dendritic cells, and shift immune balance towards Th-1 responses. Additional claims specify administration of tumor or microbial antigens, including anthrax and melanoma antigens, and use in humans, highlighting the broad applicability and method variations encompassed by the invention.
Stated Advantages
Enhancement of an antigen-specific immune response quantitatively and qualitatively, including increased cytokine production, lymphocyte activation, and antibody production.
Shift of immune response balance towards a Th-1 pro-inflammatory type, which is more effective in combating certain diseases such as cancer.
Activation and recruitment of dendritic cells, improving antigen presentation and immune activation.
Potential nontoxicity due to the endogenous nature of HMGN polypeptides, suggesting safety in therapeutic use.
Documented Applications
Treatment or prevention of diseases associated with diminished or polarized immune responses, especially cancer, including various tumor types listed in the document.
Use in vaccination strategies by co-administering HMGN polypeptides with microbial or tumor antigens to enhance antigen-specific immune responses.
Suppression of immune responses in diseases characterized by heightened Th-1 immunity, including parasitic infections and inflammatory or autoimmune disorders.
Interested in licensing this patent?