The Technology
Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by offering durable responses in a subset of patients with advanced malignancies. However, most patients either fail to respond or eventually develop resistance, creating an urgent need for strategies to overcome this barrier. This technology targets a newly discovered resistance mechanism involving tumor extracellular matrix (ECM) remodeling. Anti-PD1 therapy induces CD8+ T cell–mediated expression of BMP1, which activates lysyl oxidase (LOX) and drives collagen crosslinking, leading to ECM stiffening and immune exclusion. To counter this, a first-in-class antibody-drug conjugate (ADC) was developed by coupling using a linker, an anti-PD1 antibody with a selective BMP1 inhibitor. This dual-function molecule enables immune checkpoint blockade while locally inhibiting ECM stiffening. BMP1 inhibition also reduces TGFβ activity, enhancing T cell cytotoxicity. In preclinical models of melanoma, breast, and lung cancers resistant to ICIs, the ADC improved tumor regression, T cell infiltration, and therapeutic response compared to anti-PD1 alone. This multi-modal approach offers a promising new platform for reconditioning the tumor microenvironment and restoring immunotherapy sensitivity.
Advantages
- Synergistic anti-tumor effect in PD-1–resistant cancers
- Dual action: immune checkpoint inhibition + ECM remodeling
- Enhanced T cell infiltration and activity
Applications and Opportunities
- Treatment of immunotherapy-resistant solid tumors
- Combination therapy with existing PD-1 inhibitors
- Platform for next-generation tumor microenvironment-targeting immunotherapies
Business Development Contacts