To make TCR therapy widely applicable, it is crucial to have a diverse array of TCRs that can recognize various viral or tumor epitopes in the context of different Human Leucocyte Antigens (HLAs). This is especially important in cancer treatment, where targeting multiple epitopes simultaneously can be advantageous in addressing tumor heterogeneity.

The advent of peptide major histocompatibility complex (pMHC) multimer technology has been revolutionary in T cell analysis, providing an unprecedented level of antigen specificity. Advancements in pMHC technology have further expanded the capacity for epitope discovery. Recently, barcoding of pMHC multimers with DNA oligonucleotides has enabled the simultaneous isolation of T cells with up to 1000 different epitope specificities. This multiplexed approach could significantly increase the pool of candidate TCR candidates for adoptive cell therapy that can be obtained from a single donor. A crucial step in this advancement was the development of UV-cleavable MHC ligands. With exchangeable UV-sensitive peptides, a single MHC sample can be loaded with one of thousands of different peptides to create a large pMHC multimer library in relatively short time.

In our T-cell isolation platform, we aim to leverage the power of cutting-edge pMHC technology, with a primary focus on identifying tumor-specific TCRs from the naïve T cell repertoire of healthy donors.