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HMGN polypeptides are multidomain proteins known to function by binding DNA to regulate the transcription of certain genes inside cells. However, when a HMGN polypeptide is released extracellularly, it distinctly acts as a potent activator of the immune system. Because of this activity, it has potential use as a biological therapeutic for stimulating an immune response as well as a promising target for antagonist drugs to suppress a pathological inflammatory response.
Secreted HMGN acts as a potent recruiter and activator of dendritic cells, the cell principally responsible for initiating the immune response. Furthermore, it enables dendritic cells to preferentially induce a Th1-type T lymphocyte response that leads to enduring cellular immunity. Therefore, HMGN has potential use as a clinically effective immunoadjuvant for use in vaccines against tumors and many intracellular pathogens.
Investigators at the National Institutes of Health have developed compositions and methods for using HMGN and its derivatives as immunoadjuvants in combination, as mixtures or as chemical conjugates, with microbial or tumor antigens. HMGN has the advantage of being gene encoded so it can be fused to an antigen gene to produce recombinant fusion proteins or administered as a DNA vaccine. Conversely, HMGN could be exploited as a drug target to treat diseases that would benefit from shifting away the Th1-type immune response towards a Th2-type or humoral immune response. This would be beneficial for treatment of parasitic infections and inflammatory or autoimmune disorders.
Pre-clinical data available
Yang D, et al.
The National Cancer Institute, Laboratory of Molecular Immunoregulation, seeks parties interested in collaborative research to co-develop polypeptides or antagonists for immune response regulation. Please contact John D. Hewes, Ph.D. at 240-276-5515 or firstname.lastname@example.org for more information. Click here to view the NCI collaborative opportunity announcement.
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