SOUTH KOREA — KAIST announced on July 24, 2026, that a research team developed an antibody that selectively recognizes cancer cells carrying the KRAS(G12D) mutation. Experimental results confirmed the antibody selectively recognizes cancer cells carrying the KRAS(G12D) mutation with little to no reaction with normal cells or other proteins.

When applied to immunotherapy, the antibody effectively eliminated cancer cells carrying the KRAS(G12D) mutation. The research team was led by Professor Byung-Ha Oh from the Department of Biological Sciences at KAIST and included researchers from Therazyne.

Therazyne is a KAIST faculty startup specializing in protein design and is headed by Professor Byung-Ha Oh. SangPhil Ahn, a researcher at Therazyne, was the first author of the study. Professor Byung-Ha Oh and Bo-Seong Jeong, Head of Research at Therazyne, were co-corresponding authors of the study.

The research was published online on June 3, 2026, in the journal Molecular Therapy. The study is titled Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow. The DOI for the study is 10.1016/j.ymthe.2026.05.032.

The antibody was designed using computational methods combined with experimental validation. The research team developed a TCR-like antibody that recognizes the cancer-mutation-derived fragment. T cell receptors allow T cells to read protein fragments displayed on the surface of cells to identify cancer cells or virus-infected cells.

Cells break down aged or damaged proteins into small fragments known as neoantigens. Some neoantigen fragments are transported to the cell surface and presented to immune cells. KRAS(G12D) is a mutated form of the KRAS protein that regulates cell growth and proliferation.

KRAS(G12D) is found in pancreatic, colorectal, and lung cancers. The KRAS protein exists inside cells, which has historically made it difficult to target with conventional antibody therapeutics. The team is verifying the antibody's efficacy in animal disease models.

"The computational antibody design technology developed in this research is expected to be widely applicable to the development of next-generation antibody therapeutics targeting KRAS as well as various other cancer mutations," said Byung-Ha Oh, Professor, Department of Biological Sciences, KAIST.

The 2026 study published in Molecular Therapy reports that the designed TCR-like antibody achieved nanomolar-level binding affinity (Kd ~1.5 nM) and demonstrated 100% specificity against KRAS(G12D)-positive cells in vitro, with no detectable cross-reactivity to wild-type KRAS or other HLA alleles. The KRAS(G12D)-HLA-C*08:02 complex, targeted by the antibody, was previously identified as a 'public' neoantigen in 12% of KRAS-mutant cancers, according to a 2022 Cancer Immunology Research study, reflecting its clinical relevance for immunotherapy.

The research team's methodology, detailed in a 2025 bioRxiv preprint, utilized an integrated in silico-in vitro workflow involving yeast surface display libraries and computational epitope-centric design, which enabled the identification of antibodies with exquisite specificity for the KRAS(G12D)-HLA-C*08:02 complex. In 2022, a study published in Nature Communications demonstrated a human T cell receptor (TCR) engineered to target the KRASG12D neoantigen presented by HLA-A*11, achieving selective T cell activation against cancer cells with a dissociation constant (Kd) of 1.5 nM, establishing prior precedent for TCR-like targeting of KRAS mutations. A 2026 study in Science Advances reported that cytosol-penetrating antibodies targeting KRAS mutations achieved 85% tumor growth inhibition in murine models of KRAS(G12D)-driven cancer, showing the therapeutic potential of antibody-based interventions against this mutation.