Janina Caspar, Biontech, Mainz 

T-cell receptor (TCR) engineered T cells offer an attractive option for adoptive cell therapy of various advanced cancer types. However, due to a low frequency of reactive T-cell clones, TCR-discovery from patient and healthy donor material still represents a massive bottleneck, especially for personalized TCR therapy approaches. One potential solution might be the high throughput validation of isolated and cloned TCR sequences. In order to develop therapeutic TCR products, a rapid validation of a plethora of TCRs is urgently needed. Validation of TCRs using primary PBMC derived T cells is associated with many challenges and is very time consuming. Therefore, we use an NFAT-reporter encoding effector T-cell line that helps us to overcome these difficulties and allows further assay optimization. Moreover, we customized a robotics-based automation assay platform, comprising all necessary experimental steps and devices. This high throughput TCR-validation platform, which is more cost effective and requires less hands-on time, currently enables the validation of up to 80 TCRs against 20 different tumor targets per week.