This project aims to improve chimeric antigen receptor (CAR) T cell therapy for classical Hodgkin’s lymphoma (cHL) by overcoming immune suppression driven by the tumor microenvironment (TME). We will develop an innovative strategy combining anti-CD30 CAR T cells with a signaling-deficient PD-L1 chimeric receptor (dCAR), designed to neutralize PD-1/PD-L1-mediated T cell exhaustion. A high-performance imaging platform based on supported lipid bilayer (SLB) and super-resolution microscopy will be established to visualize the architecture of the immune synapse (IS), serving as a real-time readout of CAR signaling efficiency.
Our goals are:
(i) to create an advanced IS imaging system (Task 1);
(ii) to optimize CAR designs for enhanced CTL activity and durability (Task 2);
and (iii) to evaluate the impact of dCARs on restoring T cell function in suppressive cHL TME (Task 3).
Expected outcomes include rational CAR reengineering, deeper insight into IS dynamics, and novel therapeutic strategies to improve efficacy in relapsed/refractory cHL.

Disclaimer: This project has been funded under Contract Num. 2022FFF2NF, PRIN: PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE – Bando 2022, Italian Ministry of Research