Advancements in precision cancer treatment are progressing as researchers have created an AI platform capable of customising protein components and enhancing the patient’s immune cells to combat cancer. The novel technique, published in the journal Science, illustrates for the first time the feasibility of computer-designed proteins to steer immune cells towards cancer cells using pMHC molecules.

This significantly reduces the duration required to identify effective compounds for cancer treatment from years to mere weeks.

“We are essentially creating a new set of eyes for the immune system. Current methods for individual cancer treatment are based on finding so-called T-cell receptors in the immune system of a patient or donor that can be used for treatment. This is a very time-consuming and challenging process. Our platform designs molecular keys to target cancer cells using the AI platform, and it does so at incredible speed, so that a new lead molecule can be ready within 4-6 weeks,” states Timothy P. Jenkins, Associate Professor at the Technical University of Denmark (DTU) and the study’s last author.

Precision missiles for cancer treatment

The AI platform, created by a collaboration between DTU and the Scripps Research Institute, seeks to address a significant obstacle in cancer immunotherapy by illustrating how researchers might produce targeted therapies for tumour cells while preserving healthy tissue.

T cells often recognise cancer cells by detecting specific protein fragments, termed peptides, displayed on the cell surface by molecules known as pMHCs. The use of this knowledge for therapeutic purposes is a gradual and arduous endeavour, mostly due to the variability of the body’s T-cell receptors, which complicates the development of personalised treatments.

Enhancing the immune system

The researchers evaluated the efficacy of the AI platform on the prominent cancer target, NY-ESO-1, present in several malignancies. The scientists successfully designed a minibinder that tightly linked to the NY-ESO-1 pMHC molecules. The insertion of the engineered protein into T cells resulted in the creation of a novel cell product termed ‘IMPAC-T’ cells by the researchers, which proficiently directed the T cells to eliminate cancer cells in laboratory trials.

“It was incredibly exciting to take these minibinders, which were created entirely on a computer, and see them work so effectively in the laboratory,” states postdoc Kristoffer Haurum Johansen. He is the co-author of the study and a researcher at DTU.

The researchers utilised the pipeline to create binders for a cancer target found in a metastatic melanoma patient, effectively producing binders for this target as well. This document indicates that the technology can also be utilised for customised immunotherapy targeting novel cancer antigens.

Evaluation of therapeutic interventions

An essential phase in the researchers’ innovation was the creation of a ‘virtual safety check.’ The team employed AI to evaluate their created minibinders in comparison to pMHC molecules present on healthy cells. This strategy allowed them to eliminate minibinders that could induce hazardous side effects prior to conducting any studies.

“Precision in cancer treatment is crucial. By predicting and ruling out cross-reactions already in the design phase, we were able to reduce the risk associated with the designed proteins and increase the likelihood of designing a safe and effective therapy,” states DTU professor and co-author of the paper Sine Reker Hadrup.

Five years until therapy

Timothy Patrick Jenkins anticipates that the new approach will require up to five years before it is prepared for beginning clinical trials in humans. Upon the method’s completion, the therapy procedure will mirror existing cancer therapies utilising genetically engineered T cells, referred to as CAR-T cells, which are presently employed in the treatment of lymphoma and leukaemia. Patients will initially undergo blood extraction at the hospital, akin to a standard blood test. Their immune cells will thereafter be taken from the blood sample and changed in the laboratory to incorporate the AI-designed minibinders. The augmented immune cells are reintroduced to the patient, functioning as precision-guided missiles that specifically locate and eradicate cancer cells within the body.

Original Publication
Authors: Kristoffer Haurum Johansen, Darian Stephan Wolff, Beatrice Scapolo, Monica L. Fernández-Quintero, Charlotte Risager Christensen, Johannes R. Loeffler, Esperanza Rivera-de-Torre, Max D. Overath, Kamilla Kjærgaard Munk, Oliver Morell, Marie Christine Viuff, Iñigo Lacunza, Alberte T. Damm Englund, Mathilde Due, Anant Gharpure, Stefano Forli, Carlos Rodriguez Pardo, Tripti Tamhane, Emma Qingjie Andersen, Kasper Haldrup Björnsson, Jordan Sylvester Fernandes, Lasse Frank Voss, Suthimon Thumtecho, Andrew B. Ward, Maria Ormhøj, Sine Reker Hadrup and Timothy P. Jenkins.
Journal: Science
DOI: 10.1126/science.adv0422
Method of Research: Experimental study
Subject of Research: Cells
Article Title: De novo-designed pMHC binders facilitate T cell-mediated cytotoxicity towards cancer cells
Article Publication Date: 24-Jul-2025
COI Statement: K.H.J., D.S.W., B.S., S.R.H., and T.P.J. are inventors on a patent related
to this work under filing number US 240809-P7151EP00. The remaining authors declare no
competing interests.

Original Source: https://www.science.org/doi/10.1126/science.adv0422