Bladder cancer is one of the cancer types where treatments targeting the immune system have proven the most effective. Immunologists have been interested in deciphering the role of the immune system in this cancer for a long time. Indeed, for over 40 years, intravesical instillations of BCG have been used to reduce the rate of recurrence of non-muscle invasive bladder cancer (NMIBC). More recently, it has been shown that bladder cancer responds well to PD-1 blockade. However, this is only the case for a minority of patients and there is currently no predictive biomarker of response.
There is a positive correlation between the number of mutations in the tumor and the rate of clinical responses to these treatments. In addition, there is a consensus view that tumor infiltrating CD8+ T cells play a major role in the clinical responses to PD-1 blockade, by recognizing tumor antigens. In bladder cancer, it is however not known if these T cell recognize almost exclusively mutant peptides (also called neoantigens), which are individual to each patient, or if other tumor antigens can also be targeted by T cells. Indeed, some types of tumor antigens could be shared between patients and could therefore be used to develop generic vaccines or adoptive T cell transfers.
In this workflow, we first select potentially tumor-specific CD8+ and later on CD4+ T cells that infiltrate a bladder tumor and reconstruct their T cell receptor (TCR) in a human T cell line. Next we exclude TCRs recognizing neoantigens, by screening for recognition of predicted mutant peptides from the tumor. The remaining TCRs of interest are then screened with an autologous tumor cDNA library. For this purpose, we use a novel technology called SABR (signaling and antigen-presenting bifunctional receptors).

Analysis of the immune microenvironment of human bladder carcinomas