GENERATING AN ADAPTER BASED UNIVERSAL T CELL THERAPY FOR CANCER

Abstract

T cells present a powerful tool for cancer treatment given their ability to circulate throughout the body and “seek out and destroy” tumor deposits. The infusion of cancer patients with tumor-specific T cells is now a clinically proven treatment for cancer with six currently available. Accessibility to this promising therapeutic is limited by the requirement for the per-patient and per-target manufacturing of therapeutic T cells. Conventional synthetic antigen receptors (SARs) are rigid and typically limited to one tumor target. Given the vast number of potential targets this introduces significant timing, logistic and cost challenges when applying this approach broadly. Our program seeks to overcome these challenges by creating an on demand “off-the-shelf” solution. We propose the use of Universal SARs that can be programmed with target specificity after the engineered T cells are manufactured. A universal SAR employs an acceptor moiety which binds a molecular adapter that links the T cell to the tumor. By creating a library of adapters, a T cell engineered with a single universal SAR can be directed against multiple tumor targets. We have developed molecular adapters, termed covalent immune recruiters (CIRs), that chemically link immune receptors to cancer cells. Our grand vision is an offthe- shelf engineered T cell that is purpose-built for on demand CIR-mediated targeting and a library of CIRs directed against an array of tumor targets to yield a dynamic and affordable personalized therapy.