
Michael Daskalakis
Inselspital Berne
Berne, Switzerland
Day 2 – February 6, 2025
Keynote Swiss Cytometry Society: State of the Art in Cellular Therapy
Cellular therapies have become an additional and important tool in the treatment of hematologic malignancies in the last decade. Especially Chimeric Antigen Receptor T (CAR-T) cells have played a revolutionary approach in immunotherapy to fight cancer. This treatment involves engineering a patient`s T lymphocytes to recognize and attack malignant cells more effectively. CAR-T cell therapy has shown remarkable success in treating hematologic malignancies, such as B-cell acute lymphoblastic leukemia (ALL), certain types of B-cell Non-Hodgkin lymphoma and multiple myeloma (MM). Research is extensively ongoing aiming for equal efficacy of CAR-T cell treatment in solid tumors. Also, first clinical trials have been started in autoimmune diseases like Systemic Lupus Erythematosus (SLE) or Multiple Sclerosis (MS).
During the developmental process of a CAR-T product, the patient`s own T lymphocytes are initially collected via leukapheresis in hospital and send to the site of manufacturing. Upon culturing, these cells are then genetically modified to express a specific receptor (CAR) that is targeted against a specific antigen on the cancer cells (e.g. CD19 B-cell receptor), expanded in number, and finally infused back into the patient.
CAR T cells are designed to recognize a specific antigen on the surface of the cancer cell. Upon binding to this specific antigen, CAR-T cells get activated, proliferate, and attack the targeted cancer cell. Additionally, by secreting several cytokines, they attract and activate other immune cells potentially resulting in an even more sufficient immune attack against the neoplastic cells. After infusion, the CAR-T cells can be monitored in peripheral blood by using flow cytometry or PCR techniques.
Challenges of this new treatment are the complex manufacturing processes resulting in high costs for each cell product as well as the clinical management of side effects. After infusion of CAR-T cells, patients require careful monitoring and interdisciplinary management due to potential side effects such as cytokine release syndrome (CRS) and neurotoxicity (Immune effector cell-associated neurotoxicity syndrome (ICANS)). While being a quite successful treatment option in some hematologic malignancies, there is still limited efficacy particularly in solid tumors due to factors like an impermeable tumor`s microenvironment or lack of specific target antigens.
CAR-T therapy represents a paradigm shift in cancer therapy, especially providing hope for patients with otherwise refractory diseases. After gaining now treatment experience within clinical trials and real-world-settings over the last 10 years, durable response rates up to 40% have been reported in several clinical studies for hematologic malignancies. Ongoing advancements in engineering and clinical applications aim to make this treatment safer, more effective, and accessible to a broader range of patients.