Kathleen B. Yates

Dec 4, 2023 | nature.com | Keene L. Abbott |Audrey J. Muscato |Kathleen B. Yates |Juan Dubrot |John G. Doench |Marcela V. Maus | +3 more

AbstractCAR-T therapy is a promising, novel treatment modality for B-cell malignancies and yet many patients relapse through a variety of means, including loss of CAR-T cells and antigen escape. To investigate leukemia-intrinsic CAR-T resistance mechanisms, we performed genome-wide CRISPR-Cas9 loss-of-function screens in an immunocompetent murine model of B-cell acute lymphoblastic leukemia (B-ALL) utilizing a modular guide RNA library.

Oct 4, 2023 | nature.com | Christina Baumgartner |Arvin Iracheta-Vellve |Kira E. Olander |Omar Ávila |Audrey J. Muscato |James C. Patti | +13 more

AbstractImmune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches are needed to overcome resistance1,2. The protein tyrosine phosphatases PTPN2 and PTPN1 are central regulators of inflammation, and their genetic deletion in either tumour cells or immune cells promotes anti-tumour immunity3,4,5,6. However, phosphatases are challenging drug targets; in particular, the active site has been considered undruggable.