%41%6e%74%69%62%6f%64%69%65%73
-
KAIST Gives Antibodies “Eyes” to Detect Cancer, Targeting Cancer Mutations Inside Cells
Antibodies are like “guided missiles” that find and attack cancer cells, but cancer-causing mutations inside cells have remained a “blind spot” for treatment because antibodies cannot reach them. KAIST researchers have now succeeded in precisely targeting even intracellular cancer mutations using a newly designed antibody created through computational methods. This achievement is expected to open a new path toward next-generation precision therapies for difficult-to-treat cancers, going beyond the limitations of conventional antibody treatments.
KAIST (President Choongsik Bae) announced on the 24th of July that a research team led by Professor Byung-Ha Oh from the Department of Biological Sciences, together with researchers from Therazyne, a KAIST faculty startup specializing in protein design and headed by Professor Oh, has developed an antibody that selectively recognizes only cancer cells carrying KRAS(G12D), a representative cancer-driving mutation. By combining computational antibody design with experimental validation, the team designed a new antibody that would have been difficult to develop through conventional approaches and is now verifying its efficacy in animal disease models.
KRAS(G12D) is a mutated form of the KRAS protein, which regulates cell growth and proliferation. It is one of the most common cancer-driving mutations found in pancreatic, colorectal, and lung cancers. However, because the KRAS protein exists inside cells, it has long been considered an “undruggable target” that is difficult to directly target with conventional antibody therapeutics.
The research team focused on the natural process by which cells break down aged or damaged proteins into small fragments. The KRAS(G12D) protein inside cells is also processed in this way into small protein fragments, known as neoantigens, which serve as clues that allow immune cells to distinguish cancer cells. Some of these fragments are then transported to the cell surface and presented to immune cells. By combining computational protein design with experimental screening, the team developed a TCR-like antibody that precisely recognizes only this cancer-mutation-derived fragment.
TCR, or T cell receptor, acts as a “sensor” that allows T cells, the body’s immune cells, to read protein fragments displayed on the surface of cells and identify cancer cells or virus-infected cells. The TCR-like antibody developed in this study works on a similar principle, effectively giving an antibody the “eyes” of a T cell. It was designed to selectively recognize traces of intracellular cancer mutations that conventional antibodies cannot easily access.
Experimental results confirmed that the antibody developed by the team selectively recognizes only cancer cells carrying the KRAS(G12D) mutation, while showing little to no reaction with normal cells or other proteins. When applied to immunotherapy, it was also shown to effectively eliminate only cancer cells carrying the mutation. This finding suggests the possibility of expanding antibody therapy to intracellular cancer-driving proteins that conventional antibody treatments have been unable to target. It is also expected to serve as a platform technology for developing next-generation precision antibody therapies targeting not only KRAS but also a wide range of cancer mutations.
Professor Byung-Ha Oh said, “The antibody developed in this study can selectively identify only cancer cells carrying the KRAS(G12D) mutation, demonstrating the potential for precision antibody therapeutics that minimize damage to normal cells.” He added, “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.”
Both the first author and corresponding authors of this study are KAIST-affiliated researchers. SangPhil Ahn, a researcher at Therazyne, participated as the first author, while Professor Byung-Ha Oh and Bo-Seong Jeong, Head of Research at Therazyne, jointly led the study as co-corresponding authors. The research was published online on June 3 in Molecular Therapy, a leading international journal in the field of gene and cell therapy.
Paper title: Discovery of TCR-like antibodies to the KRAS G12D neoantigen via in silico-in vitro workflow DOI: https://doi.org/10.1016/j.ymthe.2026.05.032
This research was conducted in collaboration with Therazyne and the New Drug Development Center of the Osong Biomedical Innovation Foundation, and was supported by the Ministry of Science and ICT’s Industry-Academia-Research Linked New Drug Development Program and the National Research Foundation of Korea’s Bio & Medical Technology Development Program.
2026.07.24 View 1793 -
Creation of Synthetic Antibodies: Professor Hak Seong Kim
Synthetics antibodies which can replace antibodies from humans used as ingredients of medicines have been developed. It can increase the costs to 1/100 of the current costs and is much easier to develop. It is expected that the development period will be shortened from 10 years to 5.
Prof. Hak Seong Kim from the Biology department of KAIST conducted a joint research with Prof. Dong Seob Kim to reconstruct proteins and has succeeded.
The synthetic antibody displays much strength in terms of its productivity, structural formation, and bonding capability, and is thus regarded as an ideal protein. It can replace the antigens that are currently in use. It is expected that Korea will therefore be able to lead the world market for protein medicines which is a 192trillion won industry.
The original antibody has been used for not only treating diseases, but also for various other applications in the fields of medical sciences and biology. However, it is produced through a very complex process involving the incubation of animal cells, and is therefore very expensive. Also, most antibodies are already patented by more developed countries, so a high royalty fee must be paid.
Because of this, many countries including Korea has been concentrating on developing biosimilars copying the antibody medicines for which the patents have already expired. This causes Korea to be behind in the development of antibody protein pharmaceuticals.
Prof. Kim’s research team has focused on the face that the protein existing in some eels are not antibodies but functions as one, and has been successful in developing a synthetic antibody.
The synthetic antibody can be mass produced from the colon bacillus, which allows it to be produced at 1/100 the original cost. It is in a module structure which allows the structuring of the antibody into the desired structure, enabling it to be developed into a protein-based medicine within 5 years.
Together with this, the coherence with the important antigens can be easily controlled, thus allowing for highly effective treatments, less side-effects, high security regarding heat and pH, and the immunogen levels being negligeable. This suggests a very high rate of the antibody being converted into a protein based medication.
The synthetic antibody technology has been tested as a sample for the cure for lung diseases and rheumatism and has been proven to be appropriate. Animal testing will be conducted soon.
Prof Kim said “The original antibodies had a small area allowing the bonding with antibodies, creating barriers for raising bonding strength and structuring. The newly created antibody carries only the strengths and will become a new protein based medicine purely created by Korean technology to replace the antibodies currently used in medications.”
Furthermore, he added that, “The synthesized antibody structuring and designing technology will be widely used in the areas of detecting, diagnosing, and analyzing diseases.”
At the same time, this research result has been published in the Feb 10th issue of the PNAS, and has been supported by the future promising pioneer business program held by the Ministry of Education and Technology.
2012.04.04 View 16276