– Publication describing a new technology that provides very low levels of expression of one programming module compared to another programming module1
– Method of expressing stable low levels of a toxic gene – technology deployed in Autolus’ approach for the treatment of solid tumors
– Highly restricted release of IL-12 increases CAR T activity in an immunocompetent mouse model without systemic toxicity
LONDON, March 03, 2022 (GLOBE NEWSWIRE) — Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T-cell therapies, today announced the publication of an article in Biotechnics describing a novel technology that provides very low levels of expression of one gene module, while maintaining high levels of expression of other gene modules expressed from the same promoter1.
This technical paper describes a method for achieving very low levels of transgene expression in multi-cistronic mammalian expression systems. This is achieved via the insertion of a stop codon and a translational reading motif (TRM) between the transgenes of an mRNA encoding a multi-cistronic cassette. The TRM helps suppress the stop codon, facilitating further translation of the downstream transgene at reduced levels compared to the upstream transgene. This system addresses a fundamental challenge in cell therapy when very potent receptors, cytokines or toxins are expressed which, at normal expression levels, would be harmful to patients.
“Throughout the history of gene therapy, the focus has been on designing mammalian expression cassettes that result in high levels of transgene expression,” said James Sillibourne, director of synthetic genomics at Autolus. “However, with a very potent or toxic transgene, you need a very low level of expression. Until now, no simple way to achieve this was available. Relying on known mechanisms in bacteria and viruses, we have developed a reliable way to tightly control low levels of transgene expression.”
IL-12 is a potent antitumor cytokine. However, the majority of clinical studies involving the treatment of patients with IL-12 have been associated with severe systemic side effects and significant patient toxicities.
“Our solid tumor approach combines multiple gene modules in CAR T cells to drive the desired set of properties that we believe are essential for maximizing anti-tumor activity without increasing toxicity. Selectively adjusting expression levels has become an important technology for establishing therapeutic windows,” added Martin Pule, scientific director and founder of Autolus. “In this article, we successfully applied this technology for the highly restricted release of IL-12 that increases CAR T anti-tumor activity in an immunocompetent mouse model without inducing systemic toxicity.”
1. Sillibourne JE, Agliardi G, Righi M et al. A compact and simple method for obtaining differential transgene expression by exploiting translational readout. BioTechniques doi:10.2144/btn-2021-0079 (2022) (Epub ahead of print). The full publication in BioTechniques can be viewed here.
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 wide range of proprietary and modular T-cell programming technologies, the company designs targeted, controlled and highly active T-cell therapies 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, visit www.autolus.com.
This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are statements that are not historical facts and, in some instances, may be identified by terms such as “may”, “will”, “could”, “expect”, “plan”, “anticipate” and “believe”. These statements include, but are not limited to, statements regarding Autolus’ development of the obe-cel program; the future clinical development, efficacy, safety and therapeutic potential of its product candidates, including progress, expectations for data reporting, conduct and timing and potential future clinical activity and milestones ; and expectations regarding the initiation, design and reporting of clinical trial data. All forward-looking statements are based on management’s current beliefs and assumptions and involve risks and uncertainties that could cause actual results, performance or events to differ materially from those expressed or implied by such statements. These risks and uncertainties include, but are not limited to, the risks that Autolus’ preclinical or clinical programs may not advance or result in approved products in a timely or cost-effective manner or at all; the results of the first clinical trials are not always predictive of future results; the cost, timing and results of clinical trials; that many product candidates may not become approved drugs in a timely or cost-effective manner, if at all; the possibility of enrolling patients in clinical trials; potential safety and efficacy issues; and the impact of the ongoing COVID-19 pandemic on Autolus’ business. For a discussion of other risks and uncertainties, and other important factors, each of which could cause Autolus’ actual results to differ materially from those contained in the forward-looking statements, see the section entitled “Risk Factors” in the Autolus’ annual report on Form 20-F filed with the Securities and Exchange Commission on March 4, 2021, together with discussions of potential risks, uncertainties and other important factors in Autolus’ subsequent filings with the Securities and Exchange Commission. All information in this press release is as of the date of publication, and Autolus undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except if required by law.
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Susan A. Noonan
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