Date: 2015-05-07
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of results in Cell Reports and in Science and Translational Medicine
Company: Aduro Biotech (USA - CA)
Product: synthetic cyclic dinucleotide (CDN) molecules
Action
mechanism: immunomodulating agent/dinucleotide. Cyclic dinucleotides (CDNs) are small molecules – naturally expressed by bacteria and immune cells – that are known to activate the STING (Stimulator of Interferon Genes) signaling pathway in immune cells. STING is known to be a central mediator of innate immune response and, when stimulated, induces the expression of various interferons, cytokines and T cell recruitment factors that amplify and strengthen immune activity. Aduro’s proprietary CDN product candidates are synthetic small molecule immune modulators that are designed to target and activate the STING receptor. Once activated, the STING receptor initiates an innate immune response through multiple pathways, inducing the expression of a broad profile of cytokines, including interferons and chemokines. This subsequently leads to the development of an effective tumor antigen-specific T cell adaptive immune response.
Disease: metastatic cancers
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On May 7, 2015, Aduro Biotech announced two publications in prestigious peer-reviewed journals highlighting the anti-tumor activity of its synthetic cyclic dinucleotide (CDN) molecules when used to treat aggressive metastatic cancers in preclinical models. The journal articles in Cell Reports and in Science and Translational Medicine showcase the ability of Aduro\'s CDN molecules to specifically target the human STING pathway, which when activated, have been shown to initiate broad innate immune responses that lead to effective and specific adaptive immune responses. Cell Reports\' publication is entitled \"Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity\". The researchers demonstrated that injecting tumors with ADU-S100 induced profound regression of established melanoma, colon cancer and breast cancer tumors in mice, both in the injected tumors and distal, untreated lesions. Importantly, treatment of a single tumor initiated a systemically effective T cell response that prevented outgrowth of untreated tumors in other areas of the body (metastases). The ADU-S100-initiated response was durable, and provided long-lived immunologic memory and lasting anti-tumor protection. A second peer-reviewed journal article on Aduro\'s CDN molecules, entitled \"STING agonist formulated cancer vaccines can cure established tumors resistant to PD-1 blockade,\" was published on April 15, 2015 in Science and Translational Medicine. The data demonstrate that the increased anti-tumor activity of GVAX cancer vaccines formulated with Aduro\'s CDN molecules was STING-dependent and correlated with increased activation of dendritic cells and antigen-specific CD8+ T cells. In addition, tumors in treated mice showed significant up-regulation of PD-L1. Further, the data showed that the combination therapy of CDN molecules formulated with GVAX cancer vaccines and antibodies blocking the PD-1 immune checkpoint induced significant regression or elimination of established tumors which had not responded to treatment with anti-PD-1 inhibitors alone. On March 30, 2015, Aduro and Novartis announced a major collaboration to develop the CDN platform targeting the STING pathway for oncology.
