Granulysin is a cytolytic and proinflammatory molecule expressed by activated human cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. It has been implicated in many of diseases including infection, cancer, transplantation, autoimmunity, skin and reproductive maladies. Small synthetic forms of granulysin are being developed as novel antibiotics and studies suggest that granulysin may be a useful diagnostic biomarker and/or therapeutic for a wide variety of diseases.
The invention relates to methods of stimulating or enhancing an immune response using 15 kD granulysin. Investigators at the NIH have discovered that 15 kD granulysin (but not 9 kD granulysin) activates monocytes and induces them to differentiate into mature dendritic cells and activates allospecific T cells. This activation and subsequent differentiation induced by 15 kD granulysin may prove important in inducing or regulating immune responses in a host. Consequently, this invention could be used to treat tumors and infections, particularly as an adjuvant for vaccines and immunotherapies. Further, this technology could be used to treat autoimmune disorders and organ transplant rejection.
The National Cancer Institute, Laboratory of Cellular and Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology.
• Stimulating immunity to vaccinations, tumors or infections
• Blocking the induction of an immune response in an autoimmune disease or organ transplant rejection
• An immune response activator with broad applicability to the treatment of several diseases, including cancer, atherosclerosis, diabetes, autoimmune disorders, allergies, and infections
• Co-administering 15kD granulysin could increase the efficacy of vaccines and immunotherapeutics
Alan M Krensky (NCI), Carol Clayberger (NCI)
Stenger S, et al. An antimicrobial activity of cytolytic T cells mediated by granulysin. [PMID 9756476]
Castiello L, et al. 15 kDa Granulysin versus GM-CSF for monocytes differentiation: analogies and differences at the transcriptome level. [PMID 21501511]
Tewary P, et al. Granulysin activates antigen-presenting cells through TLR4 and acts as an immune alarmin. [PMID 20660289]
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