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SB 11285, A Novel STING Agonist that Self-Assembles into Nanostructures, is a Highly Potent Immuno-Therapeutic Agent for Cancer

Tuesday, 29 October 2019 at 12:00

Add to Calendar ▼2019-10-29 12:00:002019-10-29 13:00:00Europe/LondonSB 11285, A Novel STING Agonist that Self-Assembles into Nanostructures, is a Highly Potent Immuno-Therapeutic Agent for CancerImmuno-Oncology Europe 2019 in Rotterdam, The NetherlandsRotterdam, The NetherlandsSELECTBIOenquiries@selectbiosciences.com

Immunotherapy has emerged as a transformative approach for the treatment of cancer.  Recent work has highlighted a significant role for Stimulator of Interferon Genes (STING) agonists in immunotherapy. Conceptually, the activation of STING pathway in immune cells in the tumor microenvironment and/or tumor cells could result in the induction of innate and adaptive immunity for anti-tumor activity.

SB 11285, a synthetic cyclic dinucleotide, is a first-in-class STING agonist engineered for self-assembly into nanostructures and enhanced uptake by immune cells. SB 11285 has demonstrated highly potent, and durable antitumor activity when administered by intravenous, intraperitoneal and intratumoral routes in subcutaneous and orthotopic tumor models including A20 lymphoma, 4T1 breast cancer, B16F10 melanoma, NBT-II bladder cancer, as well as, CT26, and MC38 colon cancer models. The enhanced anti-tumor activity of SB 11285 in combination with other anti-cancer agents such as cyclophosphamide, anti-CTLA and anti-PD-1 antibody has also been demonstrated in MC38 colon carcinoma, A20 lymphoma, and CT26 colon carcinoma syngeneic mouse tumor models. The STING-mediated anti-tumor activity of SB 11285 is characterized by the induction of immune memory and abscopal effects and is consistent with the activation of innate and adaptive immunity by SB 11285. Thus, pharmacodynamic studies in syngeneic mouse tumor models revealed that administration of SB 11285 resulted in the induction of cytokines such as IFN, IL-10, and IL-12p70 at the site of the tumor, and periphery, as well as, the induction of increased numbers of several effector immune cell types including CD8+ T-cells. Furthermore, a reduction in the number of suppressive immune cell types, including granulocytic myeloid-derived suppressor cells, as well as, reduction of Treg cells at the site of the tumor were observed. Ex-vivo analysis using ELISPOT assays of spleen samples from SB 11285-treated mice in the CT26, B16F10 syngeneic mouse models, demonstrated that there was a tumor-specific IFN? T cell response following IT or IV dosing. In the CT26 colon carcinoma syngeneic mouse model, depletion of CD+T cell function by administration of anti-CD8 antibody, significantly diminished the antitumor activity of SB 11285. Overall, these data are all consistent with the anti-tumor activity of SB 11285 being mediated by the activation of STING and the priming and amplification of cytotoxic CD8+ T cells, as well as, the activation of NK cells and Th-1 macrophages, which is consistent with the induction of innate and adaptive immune system. These preclinical studies have enabled the advancement of SB 11285 towards clinical trials.