Innovative Dual Action Immunotherapy Enhances CAR-T Cell Treatment for B-ALL

B-cell acute lymphoblastic leukemia (B-ALL), the most prevalent cancer in children, accounts for approximately 85% of pediatric leukemia cases. In 2025, over 400 new cases are expected to be diagnosed in Spain alone, with about 20% of patients not surviving beyond five years, highlighting the urgent need for improved therapies.

Recent advancements in immunotherapy targeting the CD19 protein, present on B-ALL cells, have revolutionized treatment options, delivering significant clinical responses, especially in relapsed or treatment-resistant cases. However, roughly half of these patients experience relapse over time, often due to the cancer cells losing CD19 expression, a phenomenon known as immune escape.

Addressing this challenge, researchers at the Josep Carreras Leukemia Research Institute and Hospital 12 de Octubre—CNIO developed a novel CAR-T cell therapy designed to maintain effective control over leukemic cells for extended periods. Led by Dr. Pablo Menéndez, Dr. Clara Bueno, and Dr. Luis Álvarez Vallina, the team engineered a dual-targeting approach that focuses not only on CD19 but also on CD22, another protein found on B-ALL cells.

This innovative strategy involves modified T-cells expressing a CAR against CD22 to direct the immune cells toward leukemic cells. Additionally, these T-cells secrete a bispecific antibody that attracts extra T-cells, whether CAR-T or natural, to the tumor site, amplifying the immune response. By combining two targeting mechanisms—direct CAR recognition and antibody-mediated recruitment—the therapy enhances the detection and destruction of cancer cells.

Preclinical experiments demonstrated that this combined approach significantly improves the immune system’s ability to identify and eliminate leukemic cells, potentially reducing relapse rates and prolonging remission. The research, published in the Journal for Immunotherapy of Cancer, was co-authored by Javier Arroyo Ródenas and Aïda Falgàs.

This groundbreaking methodology represents a promising step toward next-generation immunotherapies targeting B-ALL, aiming to improve long-term outcomes and minimize the risk of immune escape. As further studies progress, this approach could become a key tool in the fight against resistant leukemia cases.