On May 2, 2022 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the presentation of three novel cell programming approaches at the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper) being held May 16-19, 2022 (Press release, Autolus, MAY 2, 2022, View Source [SID1234613414]).

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"The data we are presenting showcases our industry leading T cell programming technologies," said Dr. Martin Pule, Autolus’ Chief Scientific Officer. "As we seek to broaden the use of T cell therapy, we understand the CAR itself is not the sole component – instead it’s a combination of targeting, control and activity enhancements, and by improving each element we hope to ultimately improve patient outcomes in a much broader set of indications."

Posters to be presented:

1.Title: Enhancing CAR T Cell Therapy Using Fab Based Constitutively Heterodimeric Cytokine Receptors
Authors: Righi M., Srivastava S., Grothier T., Robson M., Kokalaki E., Isaac G., McKenzie C., Sillibourne J., Thomas S., Cordoba S., Pule M.
Poster Board Number: W-222
Session Date/Time: Wednesday May 18, 2022 5:30 PM – 6:30 PM
Abstract number: 1096
Summary: One of the challenges of targeting some solid tumors effectively with CAR T therapies is the harsh, immunosuppressive microenvironment of the tumor which can lead to poor persistence and a weak anti-tumor activity. Co-administration with cytokines is known to boost T cell activity and persistence, but its systemic or local administration can be toxic. We have therefore developed a versatile constitutive cytokine receptor (CCR) system which recapitulates cytokine signaling by heterodimerization of cytokine receptors, whist avoiding the potential for toxicities. These FabCCR modules signal exclusively to the CAR T cells with the potential to improve T cell therapies (TILs, TCR T cells and CAR T cells) and avoid systemic toxicity, whilst the versatility of the technology allows a broader application in cellular engineering.

2.Title: CAR T cells engineered to express a Fas-CD40 chimera display superior persistence and tumor cytotoxicity
Authors: McKenzie C., El-Kholy M., Parekh F., Lamb K., Allen C., Sillibourne J., Robson M., Thomas S., Cordoba S., Pule M.
Poster Board Number: W-231
Session Date/Time: Wednesday May 18, 2022 5:30 PM – 6:30 PM
Abstract number: 1105
Summary: Engineered T cells have shown remarkable efficacy against hematological cancers, but their effectiveness in solid tumors has been limited by inhibitory receptors expressed by the tumor or its microenvironment. One such inhibitory receptor is FasL, which binds to the Fas/CD95 receptor on the surface of an activated T cell and triggers the T cell to die by apoptosis. We have identified a Fas-CD40 chimeric protein that is able to not only rescue FasL-mediated T-cell apoptosis, but also elicit superior proliferation and anti-tumor cytotoxicity in the presence of FasL. Our 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.

3.Title: Development of a minocycline mediated protein-protein displacement platform using an anti-minocycline single domain antibody and a dedicated displaceable peptide
Authors: Jha R., Kinna A., Ferrari M., Bughda R., Ilca T., Cordorba S., Onuoha S., Thomas S., Pule M.
Poster Board Number: M-192
Session Date/Time: Monday May 16, 2022 5:30 PM – 6:30 PM
Abstract number: 311
Summary: CAR T therapies carry the inherent risks of toxicities mediated by the rapid activation of the CAR T cells in the presence of high levels of tumor. The ability to selectively control and tune down CAR T cells activation is highly desirable in order to control potential toxicity whilst maintaining anti-tumor activity. We have developed a novel, minimally immunogenic, small-molecule control system, controllable with the well-tolerated, and widely available antibiotic minocycline. Control systems such as this permit increased safety and control of engineered cell therapies: it makes the therapy tunable, dose dependent and reversible, and thus has applicability in a range of cell therapy approaches.