MT-PoINT · Motif in T cells for the Prediction of INTeractions
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-07-01 → 2023-06-30
- EU contribution
- €191,149
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
Motif in T cells for the Prediction of INTeractions
T cells, an essential part of our cellular immune response, have a critical responsibility in defending our bodies against harmful invaders such as viruses, bacteria, and even cancer cells. By continuously patrolling our body, they can recognize molecular fragments presented by infected or cancerous cells (the so-called epitopes) and initiate a response to eliminate them. In the field of cancer immunotherapy, new innovative treatments involve engineering or stimulating specific T-cells in the laboratory and then injecting them into cancer patients in order to target and destroy tumoral cells. These groundbreaking therapies have revolutionized cancer treatments, offering long-term advantages to a considerable portion of patients, including those with advanced-stage cancers. Despite considerable research, our understanding of the exact mechanisms by which T cells identify and eradicate cancerous or infected cells remains incomplete, hindering the developments of treatments that utilize or modify T cells to selectively target particular cells. The ultimate goal of the MT-PoINT project has been to develop computational models that can predict if a given T cell would recognize epitopes presented by cancerous or infected cells, and eventually eliminate them. Recent years have witnessed the emergence of a variety of immune assays that allow to isolate and sequence T cells paired with the cognate epitopes. Combining publicly available and in-house generated data with innovative algorithmic developments, we developed TCRpred: a deep-learning software that takes the T cell and the epitope sequence as inputs and predicts the likelihood of their interaction. Through a comprehensive analysis, we evaluated the precision and limitations of our tool, and used it to gain deeper insights into T cell-epitope recognition mechanism. TCRpred can serve as a valuable tool for scientists, enabling them to gain deeper insights into T cell-mediated immunity and, in turn, greatly expedite advancements in cancer immunotherapy clinical research and development.
Data: CORDIS, © European Union
Project objective
T cells are a key element of the human immune system. Upon binding to antigenic peptides (called T cell epitopes), T cells can induce the death of infected cells or prime and regulate other immune cells. In cancer immunotherapy treatments, T cells are genetically re-engineered to recognize cancer epitopes and destroy malignant cells. Unfortunately, it still remains challenging to determine which T cells can target a specific epitope, both from a computational and experimental point of view. This limits mechanistic understanding of T-cell-mediated immunity and translational applications for disease treatments.Thanks to advances in high-throughput sequencing technologies, sequence data of T cells coupled with their cognate epitopes are accumulating at an unprecedented pace, offering unique opportunities to develop data-driven T cell-epitope interaction predictors.The goal of the MT-PoINT project (Motif in T cells for the Prediction of INTeractions) is to identify patterns in T cells sequences that underlie the binding specificity, interpret them at the structural level, and to develop sequence-based predictors of T cell-epitope interactions (Aim1) with a special focus on T cells targeting cancer epitopes (Aim2). My project will capitalize on a unique dataset of publicly available and in-house generated data that was not available in previous studies, and T cell sequence data from cancer patients of Lausanne University Hospital will allow me to benchmark the in-silico predictors in a clinically relevant setting. Accurate predictions of TCR-epitope interactions can narrow down the list of T cell candidates for personalized cancer immunotherapies, and significantly accelerate cancer immunotherapy clinical developments.
Original text from CORDIS.
Participants
- UNIVERSITE DE LAUSANNE · LAUSANNECoordinatorSwitzerland
Links
Data: CORDIS, © European Union