Development of alternative CAR constructs targeting refractory B-cell neoplasms (ALTERCAR)

The goal of the ALTER CAR project is to develop new and alternative therapeutic approaches based on chimeric antigen receptors (CARs) for poor prognosis leukemia and lymphoma patients.

The cooperation within the Consortium provides a unique opportunity to implement CAR T technology in Poland and to develop alternative CAR T lymphocytes with new specifics, which may be a significant progress in CAR therapy. The long-term result of the project will be the creation of a permanent Polish-Norwegian network for the development, production and preparation of CAR-based therapies and other adoptive therapies for clinical trials in various forms of cancer.

In the first phase of the project, we will use a combined bioinformatics-transcriptomic-proteomics approach to select new targets for CAR T immunotherapy using established tumor cell lines. Selected antigens will be further tested in detail in primary cells isolated from patients with acute lymphoblastic leukemia and lymphoma refractory to standard therapy. 2-4 antigens will be selected for CAR therapy, which will be used in the second stage of the project to design a panel of CAR constructs. The initially designed construct will be optimized for affinity, and in the next phase of the project it will be validated in preclinical conditions using well-established in vitro and in vivo models.

In the final step, selected CAR candidates will be produced as GMP-grade RNA for the first human study. The end product of this proposal will be one or more alternative CARs for use in the treatment of patients with B-cell malignancies that are refractory to all treatment options or who have relapsed after prior therapies.