Research Projects

The efficacy of CAR T cell therapy is limited by antigen escape, a process by which heterogeneous tumor antigen expression leads tumors to resist targeting by CARs. Additionally, the immunosuppressive tumor micro-environment further reduces the anti-tumor activity of T cells. We are applying our pooled screening approach to develop novel synthetic receptors that overcome these limitations.

Schematic showing the seamless combinatorial gene assembly protocol in which sequentially cloned CAR domains generate hundreds of distinct full CAR constructs with unique predetermined barcodes

The efficacy of CAR T cell therapy is limited by antigen escape, a process by which heterogeneous tumor antigen expression leads tumors to resist targeting by CARs. Additionally, the immunosuppressive tumor micro-environment further reduces the anti-tumor activity of T cells. We are applying our pooled screening approach to develop novel synthetic receptors that overcome these limitations.

Illustration of a chimeric antigen receptor (CAR)

We developed a method to generate DNA libraries that encode thousands of distinct CAR domain combinations, each uniquely tagged with a DNA barcode. Quantifying the DNA barcodes via next-generation sequencing allows us to simultaneously evaluate thousands of CARs in a single dish, significantly accelerating identification of the most effective CARs.

Lymphoma xenograft NSG mouse model showing how newly discovered CARs significantly reduce tumor progression