Preclinical data presented regarding feasibility and efficacy for AUTO6NG in solid tumor indication
LONDON, Nov. 09, 2019 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies for the treatment of cancer, today presented pre-clinical data on AUTO6NG, the company’s next generation GD2-targeting CAR (chimeric antigen receptor) T cell therapy, at the 34th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) being held November 6-10, 2019, in Washington, D.C.
“Autolus’ growing set of programming modules addresses a range of inhibitory factors within the highly complex and dynamic solid tumor microenvironment. This presentation demonstrates the utility of three modules added to the clinically active and validated AUTO6 GD-2 targeting CAR that not only improve CAR T persistence but also combat the immunosuppressive environment,” said Dr. Christian Itin, chairman and chief executive officer of Autolus. “Based on these encouraging pre-clinical results, which demonstrate the activity of AUTO6NG, we plan on initiating a clinical study in patients with GD2 positive tumors including refractory/relapsed neuroblastoma in the second half of next year.”
AUTO6NG: Next generation GD2-targeting CAR T-cell therapy with improved persistence and insensitivity to TGFBeta and checkpoint inhibition for relapsed/refractory neuroblastoma, Achkova, D., et al. (Abstract number P146, poster presentation,7:00 am – 8:30 pm Eastern Time on Saturday, November 9)
AUTO6 had previously shown clinical responses without inducing neurotoxicity in pediatric patients with r/r neuroblastoma (Straathof et al., AACR 2018). Building on AUTO6, additional programming modules were introduced forming AUTO6NG to help the CAR T cells persist in and withstand the hostile tumor microenvironment. AUTO6NG is a GD2-targeted CAR T transduced with modules encoding either an IL7 chimeric cytokine receptor (IL7R_CCR) to increase persistence, or a dominant negative TGFβRII (dnTGFbRII) protein to block inhibitor signals from TGFβ and a truncated SHP2 (dSHP2) protein designed to block inhibitor signals from PD1. Both single and dual transduced CAR T cells were evaluated in vitro for anti-tumor activity, cytokine secretion, T cell proliferation, survival and resistance to immunosuppressive pathways. The addition of IL7R_CCR, dnTGFbRII and dSHP2 modules to the AUTO6NG product augment its functions by extending T-cell persistence and rendering modified T-cells resistant to TGFβ- and PD1/PDL1-driven immune inhibition in vitro. Additionally, intravenous delivery of AUTO6NG in NSG mice with established tumor burden exhibited potent anti-tumor activity and extended survival, whereas AUTO6 showed no activity in that model.
AUTO6NG is a next generation programmed T cell product candidate in pre-clinical development. AUTO6NG builds on preliminary proof of concept data from AUTO6, a CAR in clinical development for the treatment of neuroblastoma, which can target GD2-expressing cancers with a chimeric antigen receptor (CAR). AUTO6NG incorporates additional cell programming modules to augment its functions by extending persistence and rendering modified T-cells resistant to immune inhibition. With the enhanced properties of AUTO6NG, it may be suitable for the treatment of GD2-expressing solid tumors, including neuroblastoma, osteosarcoma, melanoma, small cell lung cancer, and soft tissue sarcoma.
About Autolus Therapeutics plc
Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit www.autolus.com.
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