Applications of T-cell receptor specificity annotation models for quality control and immunomonitoring in adoptive T-cell therapies

Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) is a powerful candidate immunotherapy. However, the personalized production process that underlies its potential also introduces an element of stochasticity, where the actual target of the TILs is variable across patients and protocols, and remains largely unknown. In this letter, we describe a proof-of-concept application of T-cell receptor (TCR) sequencing in combination with computational tools for annotating epitope-specificity of the TCR repertoire of TIL products as a potent quality control. We highlight the potential of this approach by demonstrating the tumor antigen-specificity of TCR clusters within the TIL product in silico , and validating these responses in vitro . We also demonstrate screening for off-cancer reactivity against viral antigens, and immune monitoring of identified TCR clones.