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

Abstract 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 the 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. Highlights T-cell receptor sequencing combined with epitope annotation tools are viable for quality control of TIL products by identifying tumor-specific clones. We showed the additional utility of screening for off-cancer reactivity, such as viral antigens. The identified tumor-specific TCR clones can be tracked in vivo providing a means of immune monitoring.