Episode 69: Novel bispecific T-cell engagers overcoming acquired EGFR resistance

Episode 69: Novel bispecific T-cell engagers overcoming acquired EGFR resistance

From Science TLDR by Raymond Ruff

May 25, 2026 · 22 min · Episode 69

About this episode

This episode discusses a study on engineered antibodies that overcome resistance to EGFR-targeted therapies in cancer treatment.

**Monday Immune Engager** — our weekly pick from the latest immune-engager digest. **Paper:** [Novel bispecific T-cell engagers overcoming acquired EGFR resistance](https://doi.org/10.1080/19420862.2026.2674236) **Authors:** Lennart Kühl, Ann-Kathrin Löffler, Oliver Seifert, Dennis Michler, et al. **Journal:** mAbs, 2026 **Why it matters:** Acquired resistance to EGFR-targeted antibody therapies remains a major barrier in colorectal and head-and-neck cancers, and this study presents an engineered antibody-based approach that circumvents both extracellular receptor mutations and downstream signaling bypass. --- **Summary** EGFR (epidermal growth factor receptor) is a well-validated oncology target, but monoclonal antibodies like cetuximab frequently lose efficacy as tumors acquire missense mutations — single amino acid substitutions such as S492R and G465R — in the extracellular domain where cetuximab binds. To find antibodies that could sidestep these escape variants, the researchers screened a human antibody phage display library against mutant EGFR protein, identifying an initial hit (A7) and then improving its binding roughly eightfold through VL shuffling (systematically…

More episodes of Science TLDR

Explore listener stats, chart rankings, contacts and more on the Science TLDR podcast page.