The work plan of the ALTER-CAR Project consists of four parallel work packages:
Work Package 1 (WP1) - Selection of the optimal targets for CAR therapy
Work Package 2 (WP2) - Designing a panel of CAR candidates targeting selected antigens
Work Package 3 (WP3) - Pre-clinical validation of generated CAR candidates
Work Package 4 (WP4) - Preparation of the material and documentation for the clinical testing
In the first stage of the project (WP1), we will employ a combined bioinformatics-transcriptomic-proteomic approach to select new targets for CAR T cell immunotherapy using established tumor cell lines. Chosen antigens will be further extensively validated in primary cells isolated from acute lymphoblastic leukemia and lymphoma patients refractory to standard-of-care treatment. As a result of WP1, we will select 2-4 antigens as candidates for CAR therapy, which in the second stage of the project (WP2) will be used for designing a panel of CAR constructs. The initially designed construct will be affinity-optimized and in a subsequent stage of the project (WP3) validated in pre-clinical settings using well-established in vitro and in vivo models. In a final stage (WP4), selected CAR candidate/s will be manufactured as GMP-grade RNA for the first-in-man study. The final product of this proposal will be one or more alternative CARs to be used in the treatment of patients with B cell malignancies refractory to all treatment options or patients who relapse after previous therapies.
The subsequent stages of the project are illustrated below:
