Cibisatamab and FAP-4-1BBL Show Activity in Refractory Colorectal Cancer

Metastatic colorectal cancer remains a leading cause of oncology-related mortality, with five-year survival rates for advanced disease stagnating between 10% and 25% [1]. While immune checkpoint inhibitors have transformed outcomes for patients with high microsatellite instability, these benefits are largely absent in the 90% of patients with microsatellite-stable disease [2]. This resistance is primarily driven by an immunosuppressive tumor microenvironment and a lack of effector T cell infiltration, often referred to as a cold tumor phenotype [3, 4]. Bispecific T cell engagers designed to bridge CD3-positive T cells with tumor-associated antigens like carcinoembryonic antigen represent a strategy to force immune recognition, yet their efficacy as monotherapy has been limited by incomplete T cell activation and the absence of necessary co-stimulatory signals [5, 6]. A new study now evaluates whether adding a localized co-stimulatory agonist can bridge this therapeutic gap and sensitize these recalcitrant tumors to T cell-mediated destruction.