Selective inhibition of TGFβ1 activation overcomes primary resistance to checkpoint blockade therapy by altering tumor immune landscape
Constance J. Martin, Abhishek Datta, Christopher Littlefield, Ashish Kalra, Christopher Chapron, Stefan Wawersik, Kevin B. Dagbay, Christopher Brueckner, Anastasia Nikiforov, Francis T. Danehy, Frederick C. Streich, Christopher Boston, Allison Simpson, Justin Jackson, Susan Lin, Nicole Danek, Ryan Faucette, Pichai Raman, Allan D. Capili, Alan Buckler, Gregory J. Carven, Thomas Schürpf
Abstract
T cells and decreased immunosuppressive myeloid cells. No cardiac valvulopathy was observed in a 4-week rat toxicology study with SRK-181, suggesting that selectively blocking TGFβ1 activation may avoid dose-limiting toxicities previously observed with pan-TGFβ inhibitors. These results establish a rationale for exploring selective TGFβ1 inhibition to overcome primary resistance to CBT.