Autolus Therapeutics Plc (AUTL)

[jondoeuk]

They are now working on ways to further improve ex vivo expansion (using an inhibitor of the PI3K/AKT/mTOR pathway, platelet lysate and/or IL-21 [1-7]), as well as engineering some their CAR-T cell products to locally secrete anti-ectoenzyme antibodies to either CD39* and CD73*, and/or GSI**.

Refs:
1 https://www.nature.com/articles/s41375-017-0008-6
2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6895454/
3 https://jitc.biomedcentral.com/articles/10.1186/s40425-019-0804-9
4 https://www.hindawi.com/journals/jir/2019/3616120/
5 https://www.jimmunol.org/content/173/2/900.long
6 https://www.jimmunol.org/content/178/12/7640.long
7 https://ashpublications.org/blood/article/111/1/229/107909/IL-21-mediated-Foxp3-suppression-leads-to-enhanced

* High adenosine (ADO) in the tumour microenvironment suppresses the immune response by inhibiting antitumour immune functions (cytotoxic and effector functions of T- and NK cells) and promoting the development of immunosuppressive cells (Tregs, MDSCs, TAMs and/or tolerogenic DCs). Extracellular ADO can be generated from ATP released by cancer cells undergoing stress and/or death through the combined actions of CD39 (ATP to AMP) and CD73 (AMP to ADO).

** https://ashpublications.org/blood/article/134/19/1585/374996/Secretase-inhibition-increases-efficacy-of-BCMA https://ashpublications.org/blood/article/134/Supplement_1/1856/427564/Response-to-Bcma-CAR-T-Cells-Correlates-with