Guiding Antiviral Cell Therapy Approaches with an Online Resource of Clinically Scored Epitopes, T-Cell Receptors, and B-Cell Receptors.

Introduction: The clinical application of cell-based immunotherapies is a rapidly emerging field, and recent advances in gene therapy have opened up a new era of innovative treatment approaches. Introducing a specific T-cell receptor (TCR) against viral epitopes or chimeric antigen receptor (CAR) into T cells and effector cells allows reprogramming of their specificity and utilization for advanced therapeutic applications in infectious diseases and virus-induced malignancies. Many technologies have been developed to genetically engineer T cells, and existing databases in silico predict or describe identified viral epitopes, TCRs, or B-cell receptors (BCRs). However, their therapeutic application is still hampered by limited knowledge on their clinical impact. Methods: An open-access online resource was developed, integrating a data-mining algorithm scoring the epitopes, TCRs, and BCRs (ETB database) according to clinical evidence. Results: We hereby present a new level of clinical evidence-based knowledge transfer for selecting individual protective TCRs or BCRs for therapeutic application. The database is publicly available at https://app.bitcare.de/epitopeFrontend/. Conclusion: Redirecting T-cell specificity by genetic engineering using clinically protective TCR or CAR sequences will not only bring significant progress to the field of adoptive T-cell therapies but also lay the groundwork for broader applications such as off-the-shelf approaches.