Immunotherapy has been a great hope for patients with multiple myeloma, since this type of blood cancer has previously been considered incurable. Specifically, CAR-T therapy treatments are available for use after clinical trials. These CAR-T immunotherapies are getting very good results in the remission of multiple myeloma. However, the treatment’s effectiveness decreases in many patients over time, leading to relapses. Thus, a study supported by the Spanish Association Against Cancer (AECC) has achieved a new strategy in laboratory models to lengthen the effectiveness of these CAR-T treatments and thereby prevent relapses. The study was conducted by the team of Carlos Fernández de Larrea, a haematologist at Hospital Clínic and the head of IDIBAPS’ Myeloma, amyloidosis macroglobulinemia and other gammapathies research group.
CAR-T immunotherapy treatments use the patient’s immune system cells, which are extracted and modified in the laboratory so they can identify and attack cancer. Healthy immune system cells normally mature over time, learning how to deal with infections and other dangers and to create memory. However, this maturation process is diminished in cells modified for CAR-T immunotherapy, which lose their function and anti-tumour efficacy over time. Fernández de Larrea’s team is working to make CAR-T immunotherapy effective for longer. They hope to do this by focusing on the Blimp-1 gene, which is known to be key to the maturation of immune system cells. In addition to modifying immune system cells so they can attack cancer, they are using the CRISPR-Cas9 gene editing technique to eliminate the Blimp-1 gene, which prolongs CAR-T cell activity in animal models. In conclusion, the results of this study provide a new strategy for boosting the efficacy of immunotherapy treatments and prevent relapse in multiple myeloma patients.
Article reference:
Battram AM, Mañé Pujol J, Moreno DF, Oliver-Caldes A, Carpio J, Cardus O, Rodríguez-Lobato LG, Urbano-Ispizua Á, Fernández de Larrea C. Genetic Disruption of Blimp-1 Drastically Augments the Antitumor Efficacy of BCMA-Targeting CAR-T Cells. Blood Adv. 2024 Dec 6:bloodadvances.2024013209. doi: 10.1182/bloodadvances.2024013209.
