Expanding the Autolus toolkit of T-cell engineering modules against complex and immunologically hostile cancers, including solid cancer applications
LONDON, April 26, 2023 (GLOBE NEWSWIRE) -- Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, today announced the publication of a paper in Molecular Therapy Nucleic Acids1, titled ‘Novel Fas-TNFR chimeras that prevent Fas ligand-mediated kill and signal synergistically to enhance CAR T-cell efficacy.’
CAR T cells have shown remarkable efficacy against hematological cancers, but their effectiveness in solid tumors has been limited by inhibitory factors expressed by the tumor or its microenvironment. One such inhibitory factor is Fas ligand (FasL), which binds to the Fas receptor (CD95) on the surface of an activated T cell and triggers the CAR T cell to die by apoptosis.
The research group at Autolus tested several Fas chimeras which consist of the extracellular domain of Fas fused to the intracellular domain from different TNF receptor superfamily members. Expression of these chimeras in a CAR T cell not only blocks apoptosis triggered by FasL, but results in co-stimulation, which promotes CAR T cell survival and proliferation.
A small subset of these chimeras, best exemplified by Fas-CD40 fusion, were found to be particularly effective at promoting CAR T cell survival and anti-tumor cytotoxicity in the presence of FasL. These data support the potential of this Fas-CD40 chimera to render T cell therapies resistant to FasL-mediated cell death and improve their effectiveness against solid tumors.
Martin Pule, Chief Scientific Officer and Founder of Autolus said, "Development of Fas-CD40 adds to our growing toolkit of T-cell engineering modules and aligns with Autolus’ strategy for increasing the Company’s capabilities, with particular application against complex and immunologically hostile cancers, including solid cancer applications.”
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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Susan A. Noonan
S.A. Noonan Communications