정보성 (테라자인) | 한빛사논문 > 한빛사

한빛사논문

조회49

테라자인

CV File

Mol. Ther., June 03, 2026 | https://doi.org/10.1016/j.ymthe.2026.05.032 Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow

SangPhil Ahn¹ ∙ Tae-Sung Oh¹ ∙ Seonghyuk Suh¹ ∙ Joon-Young Jeon² ∙ Sangjoon Lah³ ∙ Kyeongmin Ryu³ ∙ Sanghyeon Choi¹ ∙ Hyeonkyeong Kim³ ∙ Eun Gyo Lee³ ∙ Hyejin Lee¹ ∙ JooYeon Lee¹ ∙ Yoonji Kim⁴ ∙ Sanggil Kim⁴∙ So Ra Park⁴ ∙ Hojin Yoo⁴ ∙ So-Young Choi⁴ ∙ Joo Eon Lee⁴ ∙ Dong-Kyun Kim^5,6 ∙ Bo Mi Ku⁷ ∙ Wooram Jung⁸ ∙ Myung-Ju Ahn⁷ ∙ Jae U. Jung⁸ ∙ Yong-Sung Kim⁹ ∙ Byung-Ha Oh1,2 ∙ Bo-Seong Jeong¹

¹TheraZyne, Inc., Daejeon, 34051, Republic of Korea
²Department of Biological Sciences, Graduate School of Engineering Biology, KAIST Institute for BioInnovation, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea
³Bioprocess Engineering Center, Korea Research Institute of Bioscience & Biotechnology, Cheongju, 28116, Republic of Korea
⁴New Drug Development Center, Osong Medical Innovation Foundation, Cheongju, 28160, Republic of Korea
⁵KAIST Stem Cell Center, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea
⁶Graduate School of Stem Cell and Regenerative Biology, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea
⁷Division of Haematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, 06351, Republic of Korea
⁸Cancer Biology Department, Infection Biology Program, and Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, United States
⁹Department of Molecular Science and Technology, Advanced College of Bioconvergence Engineering, Ajou University, Suwon, 16499, Republic of Korea

Corresponding authors: Byung-Ha Oh∙ Bo-Seong Jeong

Abstract

Antibodies that recognize peptide-loaded class I major histocompatibility complex (MHC) molecules could enable therapeutic targeting of intracellular oncogenic proteins, yet their discovery has been hampered by the small size of peptide antigens and the need for allele-specific recognition. Here, we describe an integrated in silico–in vitro workflow for generating high-affinity, selective antibodies to KRAS G12D10 presented by HLA-C*08:02, a clinically validated cancer neoantigen. In the in silico stage, multiple human antibody-derived variable fragments optimally docked to the target were generated, followed by limited sequence design of complementarity-determining regions (CDRs). In the in vitro stage, limited CDR diversity was introduced to construct yeast surface-displayed library, which was subjected to iterative selection. This workflow yielded KRAS G12D10/HLA-C*08:02-specific antibodies with high affinity. Comprehensive specificity profiling using a phage display library confirmed no human off-target reactivity, and in silico analysis predicted low immunogenicity. When reformatted as chimeric antigen receptors or bispecific T-cell engagers, these antibodies mediated selective cytotoxicity against target-positive cells. Together, these findings establish a practical design-to-function pipeline for TCR-like antibody discovery and demonstrate the feasibility of therapeutically targeting KRAS G12D-driven malignancies.

논문정보