February 21, 2023

TCR-QR: Identifying Tumour-reactive TCRs for Personalized T Cell Therapies

5th Call, Tech Trans

Short Summary

This study will collect and analyse multi-omic (transcriptome, epigenome and immune repertoire) data from tumor infiltrating T cells (TILs). With a synthetic T cell platform, we will test their T cell receptors (TCRs) for reactivity to autologous tumor cells. Finally, functional data will be connected with multi-omic data in order to find biomarkers and predict tumor reactive T cells.

Goals

The goals of this project are to 1) Identify tumor reactive T cells across multiple patients and 2) Build a model that identifies markers and can predict additional tumor reactive T cells.

Significance

Although cancer immunotherapy has revolutionized therapeutic regimens, only a fraction of patients responds to immune checkpoint blockade or adoptive cell transfer. It is thus highly important to make therapies more personalized by identifying the fraction of tumor reactive to bystander T cells that have infiltrated the tumor. Further, being able to selectively identify tumor reactive T cells, offers more targeted adoptive cell transfer by only reinfusing product that recognizes the tumor cells. Finally, identified tumor reactive TCRs may be used in personalized transgenic T cell receptor therapies.

Background

T cells play a major role in the recent revolution of cancer immunotherapy with either genetically modified or reactivated T cells being infused into the patient, which then elicit a response against the tumor cells. Often, only a fraction of TILs in a patient are reactive to the tumor, whereas others are so-called bystander T cells. It is thus of high interest to discriminate and select mainly tumor reactive T cells for therapeutic approaches.