Episode 74: Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow

Episode 74: Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow

From Science TLDR by Raymond Ruff

June 9, 2026 · 12 min · Episode 74

About this episode

This episode discusses the discovery of TCR-like antibodies targeting the KRAS G12D neoantigen through a novel computational-experimental workflow.

**Monday Immune Engager** — our weekly pick from the latest immune-engager digest. **Paper:** [Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow](https://doi.org/10.1016/j.ymthe.2026.05.032) **Authors:** SangPhil Ahn, Tae-Sung Oh, Seonghyuk Suh, Joon-Young Jeon, et al. **Journal:** Molecular Therapy, 2026 **Why it matters:** A hybrid computational-experimental pipeline now offers a practical route to generate stable, high-affinity antibodies against intracellular oncoproteins — a class of targets that has long resisted conventional drug discovery. --- **Summary** KRAS G12D is one of the most prevalent oncogenic mutations in pancreatic, colorectal, and lung cancer, yet it sits inside the cell, beyond the reach of conventional antibody drugs. The cell's own antigen-presentation machinery offers a workaround: proteasomal degradation continuously loads short peptide fragments of intracellular proteins onto MHC class I complexes (here, HLA-C\*08:02) for display at the surface. TCR-like antibodies — synthetic immunoglobulins engineered to recognize these peptide–MHC complexes — could exploit this window, but traditional screening tends to…

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