Cancer Treatment AI Platform Designs Molecular Missiles to Attack Cancer Cells

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Technical University of Denmark

KNF Neuberger GmbH

A new method can produce custom-designed proteins in just 4-6 weeks that can arm the T cells of the body's immune system to attack and kill cancer cells.

Precision cancer treatment on a larger scale is moving closer after researchers have developed an AI platform that can tailor protein components and arm the patient's immune cells to fight cancer. The new method, published in the scientific journal Science, demonstrates for the first time, that it is possible to design proteins in the computer for redirecting immune cells to target cancer cells through pMHC molecules. This dramatically shortens the process of finding effective molecules for cancer treatment from years to a few weeks.

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“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,” says Associate Professor at the Technical University of Denmark (DTU) and last author of the study Timothy P. Jenkins.

The AI platform, developed by a team from DTU and the American Scripps Research Institute, aims to solve a major challenge in cancer immunotherapy by demonstrating how scientists can generate target treatments for tumor cells and avoid damaging healthy tissue.

Normally, T cells naturally identify cancer cells by recognizing specific protein fragments, known as peptides, presented on the cell surface by molecules called pMHCs.It is a slow and challenging process to utilise this knowledge for therapy, often because the variation in the body's own T-cell receptors makes it challenging to create a personalised treatment.

Boosting the Body’s Immune System

In the study, the researchers tested the strength of the AI platform on a well-known cancer target, NY-ESO-1, which is found in a wide range of cancers. The team succeeded in designing a minibinder that bound tightly to the NY-ESO-1 pMHC molecules. When the designed protein was inserted into T cells, it created a unique new cell product named ‘IMPAC-T’ cells by the researchers, which effectively guided the T cells to kill cancer cells in laboratory experiments.

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

The researchers also applied the pipeline to design binders for a cancer target identified in a metastatic melanoma patient, successfully generating binders for this target as well. This documented that the method also can be used for tailored immunotherapy against novel cancer targets.

A crucial step in the researchers’ innovation was the development of a ‘virtual safety check’. The team used AI to screen their designed minibinders and assess them in relation to pMHC molecules found on healthy cells. This method enabled them to filter out minibinders that could cause dangerous side effects before any experiments were carried out.

“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,” says DTU professor and co-author of the study Sine Reker Hadrup.

Five Years to Treatment

Timothy Patrick Jenkins expects that it will take up to five years before the new method is ready for initial clinical trials in humans. Once the method is ready, the treatment process will resemble current cancer treatments using genetically modified T cells, known as CAR-T cells, which are currently used to treat lymphoma and leukaemia. Patients will first have blood drawn at the hospital, similar to a routine blood test. Their immune cells will then be extracted from this blood sample and modified in the laboratory to carry the AI-designed minibinders. These enhanced immune cells are returned to the patient, where they act like targeted missiles, precisely finding and eliminating cancer cells in the body.

Original Article: De novo-designed pMHC binders facilitate T cell-mediated cytotoxicity towards cancer cells; Science; DOI:10.1126/science.adv0422

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