Clinical-stage biopharmaceutical company, Autolus, has presented data for its pan-checkpoint blocking technology at the American Society of Hematology (ASH) annual meeting in Atlanta.
Research
Cancer cells are known to use checkpoint inhibition as a defence mechanism to avoid being killed by T-cells. In the presentation, made by Autolus founder and CSO — Dr Martin Pule, it was shown that CAR T-cells expressing an engineered adapter protein designed to block PD1 and related pathways makes the CAR T-cells resistant to the cancer cell defence mechanism.
The engineered adaptor protein is a dominant negative SHP2 protein that restores CAR T-cell activation by cancer cells expressing PD-L1, which triggers the killing of cancer cells, and allows for normal proliferation of T-cells and cytokine release.
As opposed to systemic monoclonal antibody based checkpoint inhibition therapies, this strategy is confined to the engineered CAR T-cells, potentially leading to less systemic toxicity. In addition it has the potential to block a range of inhibitory signals as the adaptor proteins SHP1 and SHP2 are common to many inhibitory receptor pathways.
“This pan-checkpoint block is an example of the technologies Autolus is working on to address the layers of defence cancers are deploying to avoid killing by T-cells,” commented Dr Christian Itin, chairman and CEO of Autolus. “Use of this and additional technologies will be important for the application of CAR T therapy; not only in blood cancers, but also for the treatment of patients with solid tumours.”