Cancer

Mouse studies suggest TGFβ-RII-checkpoint inhibitor mAb fusion proteins could help treat checkpoint inhibitor-resistant melanoma and breast cancers. The proteins consist of the TGFβ-RII ectodomain linked to mAbs targeting either CTLA-4 or PD-L1. In one or two xenograft mouse models of melanoma, TGFβ-RII fused to the anti-PD-L1 mAb or the anti-CTLA-4 mAb decreased tumor growth and numbers of Treg cells in tumors, and increased numbers of effector T cells in tumors compared with the PD-L1-targeting humanized mAb Tecentriq atezolizumab or the human CTLA-4-targeting mAb Yervoy ipilimumab. In a xenograft mouse model of triple-negative breast cancer (TNBC), the anti-CTLA-4 fusion protein decreased tumor growth and numbers of Treg cells in tumors, and increased numbers of effector T cells in tumors compared with Yervoy or Yervoy plus the PD-1-targeting humanized mAb Keytruda pembrolizumab. In the model, the anti-PD-L1 mAb-based fusion protein decreased tumor growth and numbers of Treg cells in tumors and increased numbers of effector T cells in tumors compared with Tecentriq, and decreased tumor growth compared with the PD-L1-targeting human mAb Bavencio avelumab. Next steps for Y-Trap Inc. could include testing the fusion proteins in additional models of checkpoint-inhibitor resistant melanoma and breast cancers.

Bristol-Myers Squibb Co. and Ono Pharmaceutical Co. Ltd. market Yervoy to treat melanoma and have the compound in Phase I/II testing to registration for other cancers...