Dual action immunotherapy in CAR-T cells improves control of B-cell acute lymphoblastic leukemia progression

B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancer in children, accounting for around 85% of pediatric leukemia cases. According to REDECAN, more than 400 new cases are estimated to be diagnosed in Spain in 2025, and about 20% of patients are not expected to survive beyond five years.

On the bright side, the development of new immunotherapies directed towards the CD19 protein, present on B-ALL cancer cells, has been a game changer, reaching impressive clinical responses in patients who have relapsed or do not respond to standard treatments. However, around 50% of these patients eventually relapse, often because the cancer cells adapt by losing the CD19 marker, a process known as immune escape.

Precisely to avoid immune evasion, researchers at the Josep Carreras Leukemia Research Institute and Hospital 12 de Octubre—CNIO, tested a new CAR-T immunotherapy—using modified living immune T-cells as anticancer drugs—that can keep leukemic cells under control for longer in in vitro experiments. The team, led by Dr. Pablo Menéndez, Dr. Clara Bueno and Dr. Luis Álvarez Vallina targeted not just CD19 but also CD22, a second protein present in B-ALL cells, to increase efficiency.

While double targeting had been tested before, they combined two different methods at the same CAR-Ts to boost immune activation against cancer cells. First, the modified T-cell had a regular CAR-T construct against CD22, to drive it towards leukemic cells. On top of it, the CAR-Ts also secrete a molecule that can attract any T-cell, CAR-T or not, towards the CD19 protein, known as a bispecific antibody.

This innovative approach brings together the precision and longevity of CAR-T cells, which can seek out and destroy cancer cells throughout the body, with the power of bispecific antibodies, which help recruit other T cells to boost the anti-tumor response. As a result, leukemic cells are identified twice and by a larger number of T-cells, increasing the efficacy of the treatment, as shown in preclinical experiments.

The new methodology, published in the Journal for Immunotherapy of Cancer and co-first authored by Javier Arroyo Ródenas and Aïda Falgàs, represents a new and innovative approach that could ground a new generation of immunotherapies in the future, able to reduce relapse rates and improve long-term outcomes for patients.

B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancer in children, accounting for around 85% of pediatric leukemia cases. According to REDECAN, more than 400 new cases are estimated to be diagnosed in Spain in 2025, and about 20% of patients are not expected to survive beyond five years.

On the bright side, the development of new immunotherapies directed towards the CD19 protein, present on B-ALL cancer cells, has been a game changer, reaching impressive clinical responses in patients who have relapsed or do not respond to standard treatments. However, around 50% of these patients eventually relapse, often because the cancer cells adapt by losing the CD19 marker, a process known as immune escape.

Precisely to avoid immune evasion, researchers at the Josep Carreras Leukemia Research Institute and Hospital 12 de Octubre—CNIO, tested a new CAR-T immunotherapy—using modified living immune T-cells as anticancer drugs—that can keep leukemic cells under control for longer in in vitro experiments. The team, led by Dr. Pablo Menéndez, Dr. Clara Bueno and Dr. Luis Álvarez Vallina targeted not just CD19 but also CD22, a second protein present in B-ALL cells, to increase efficiency.

While double targeting had been tested before, they combined two different methods at the same CAR-Ts to boost immune activation against cancer cells. First, the modified T-cell had a regular CAR-T construct against CD22, to drive it towards leukemic cells. On top of it, the CAR-Ts also secrete a molecule that can attract any T-cell, CAR-T or not, towards the CD19 protein, known as a bispecific antibody.

This innovative approach brings together the precision and longevity of CAR-T cells, which can seek out and destroy cancer cells throughout the body, with the power of bispecific antibodies, which help recruit other T cells to boost the anti-tumor response. As a result, leukemic cells are identified twice and by a larger number of T-cells, increasing the efficacy of the treatment, as shown in preclinical experiments.

The new methodology, published in the Journal for Immunotherapy of Cancer and co-first authored by Javier Arroyo Ródenas and Aïda Falgàs, represents a new and innovative approach that could ground a new generation of immunotherapies in the future, able to reduce relapse rates and improve long-term outcomes for patients.