Luis Álvarez Vallina (left) and Javier Arroyo, at the Spanish National Cancer Research Centre. / Pilar Gil. CNIO
CAR-STAb immunotherapy has obtained positive results in animal models, to a great extent because it recruits more defensive cells from the body to combat the tumour cells.
“This study opens up a promising path to offer leukaemia patients more effective therapies”, according to Luis Álvarez Vallina, Head of the Cancer Immunotherapy Clinical Research Unit at the Hospital Universitario 12 de Octubre-Spanish National Cancer Research Centre (CNIO).
It has been published in the Journal for Immunotherapy of Cancer.
Immunotherapy is driving forward advances in the treatment of many types of cancer, including B-cell acute lymphoblastic leukaemia. Nowadays, cases of this type of blood cancer that fail to respond to conventional chemotherapy are being treated with immunotherapy, although it does not work in all patients.
A study proposes a new immunotherapy, which has obtained positive results in animal models. It is called CAR-STAb and its advantages include recruiting more defensive cells from the body to combat the tumour cells.
It has been developed by Luis Álvarez-Vallina, Head of the Cancer Immunotherapy Clinical Research Unit Hospital Universitario 12 de Octubre-Spanish National Cancer Research Centre (CNIO); Clara Bueno and Pablo Menéndez, from the Josep Carreras Leukaemia Research Centre. It has been published in the Journal for Immunotherapy of Cancer.
The next step in the research is a clinical trial, authorisation for which will be requested in 2026.
Bispecifics and CAR-T, in one
B-cells or B-lymphocytes are components of the immune system and their main function is to detect and combat threats to the organism. However, when they stop working properly, they are also the source of diseases such as B-cell acute lymphoblastic leukaemia (B-ALL), a very aggressive type of blood cancer. It is the most common cancer in childhood, accounting for 35% of paediatric tumours, but it affects people of all ages.
At present, the first treatment option for B-ALL is chemotherapy, based on the administration of toxic drugs that kill tumour cells. When chemotherapy does not work, immunotherapy is used, which involves activating the body’s own defences against the tumour. More specifically, bispecific antibodies are administered, which bring the defensive T-lymphocyte cells into contact with the tumour cells. Another option is CAR-T cell immunotherapy, which involves extracting T cells from the patient and modifying them in the laboratory, so that they can recognise and target tumour cells once they have been reintroduced into the patient’s body.
Both bispecific antibodies and CAR-Ts have improved the treatment in resistant cases of B-cell acute lymphoblastic leukaemia. However, some patients remain unresponsive, and more than half of those who do respond suffer relapses.
The latest study published in the Journal for Immunotherapy of Cancer presents a third pathway that combines the previous ones: a CAR-T therapy that produces a bispecific antibody.
Tumour cells that do not escape the immune system
There are several advantages. CAR-STAb lymphocytes recognise tumour cells by two different pathways, ensuring that they cannot escape. A positive feature of bispecific antibodies is added to this: their ability to recruit other unmodified T-lymphocytes present in the tumour environment and increase the number of defensive cells involved in combating the cancer.
“This is the first time that the potential of this strategy has been demonstrated in B-cell neoplasms”, explains Álvarez Vallina, who points out that “this study opens up a promising path to offer more effective therapies to leukaemia patients, especially those who are refractory or who escape control by currently available therapies.
Javier Arroyo, researcher in Álvarez Vallina’s group at the 12 de Octubre University Hospital, is the first co-author of the study, along with Aida Falgás, from the Josep Carreras Leukaemia Research Institute.
Arroyo highlights that “using different mechanisms and different targets enables the tumour cell to be subjected to immunotherapy, should it try to escape it. Therefore, it becomes more complicated for the cell to escape control by the immune system”.
Funding:
This research has been partly funded by the European Commission’s ERC programme, the Spanish Government, the regional government of Catalonia and the Community of Madrid. It has also been funded by private entities, such as the Spanish Cancer Association, the CRIS Foundation, FERO Foundation, Unoentrecienmil, Josep Carreras Leukaemia Research Institute, La Caixa Foundation social work.
Reference article
Arroyo-Ródenas J, Falgàs A, Díez-Alonso L, et al. “CD22 CAR-T cells secreting CD19 T-cell engagers for improved control of B-cell acute lymphoblastic leukemia progression”. Journal for ImmunoTherapy of Cancer 2025;13:e009048.