Targeted therapies against the epidermal growth factor receptor (EGFR) have improved treatment options for several types of cancer, including colorectal cancer. However, many tumors eventually develop resistance to these therapies, limiting their long-term effectiveness. One common mechanism involves mutations in the extracellular domain (ECD) of EGFR that prevent therapeutic antibodies such as cetuximab from binding effectively.
In the new publication, novel EGFR-targeting antibodies were developed to recognize different regions of the receptor and remain effective even in the presence of clinically relevant resistance mutations. The team further engineered these antibodies into bispecific T-cell engagers — molecules designed to simultaneously bind cancer cells and activate immune cells to destroy them.
The newly developed constructs successfully triggered T cell-mediated killing of tumor cells carrying both normal EGFR and therapy-resistant EGFR variants. Importantly, anti-tumor activity was also demonstrated in preclinical tumor models, highlighting the potential of this next-generation immunotherapy approach.
The study provides an important step toward more durable and effective treatments for patients with EGFR-positive cancers that no longer respond to currently available therapies.
Publication: Novel bispecific T-cell engagers overcoming acquired EGFR resistance (Link to full text)
Authors: Lennart Kühl , Ann-Kathrin Löffler , Oliver Seifert, Dennis Michler, Miriam Kuhlmann, Giulio Russo, Philipp Kuhn, Helena Nowack, André Frenzel, Thomas Schirrmann, Monilola A Olayioye, Roland E Kontermann
