GRATCR: Epitope-Specific T Cell Receptor Sequence Generation With Data-Efficient Pre-Trained Models

Abstract

T cell receptors (TCRs) play a crucial role in numerous immunotherapies targeting tumor cells. However, their acquisition and optimization present significant challenges, involving laborious and time-consuming wet lab experimental resource. Deep generative models have demonstrated remarkable capabilities in functional protein sequence generation, offering a promising solution for enhancing the acquisition of specific TCR sequences. Here, we propose GRATCR, a framework incorporates two pre-trained modules through a novel “grafting” strategy, to de-novo generate TCR sequences targeting specific epitopes. Experimental results demonstrate that TCRs generated by GRATCR exhibit higher specificity toward desired epitopes and are more biologically functional compared with the state-of-the-art model, by using significantly fewer training data. Additionally, the generated sequences display novelty compared to natural sequences, and the interpretability evaluation further confirmed that the model is capable of capturing important binding patterns.