2022 November 15

Unoentrecienmil awards a project for the development of an immunotherapy against one of the pediatric leukemias with the worst prognosis

The Unoentrecienmil Foundation, which promotes research projects for the complete cure of childhood leukemia, today awarded its 9th Annual Research Grant to Dr. Clara Bueno of the Josep Carreras Leukaemia Research Institute. For two years, the Doctor will carry out her work to develop new therapeutic strategies, some based on immunotherapy, against the NG2 antigen, related to relapses of B-cell Acute Lymphoblastic Leukemia with alterations in the MLL gene, and thus improve the survival rate of these patients, now at 35%.

- Dr. Clara Bueno has been the winner of the 9th edition of this Annual Grant and will carry out her work at the Josep Carreras Leukaemia Research Institute for two years, together with her co-researcher Dr. Belén López Millán.

- Thanks to the foundation's grant program, the doctor's research team, which has been working in this line for 15 years, will be able to continue their research to improve the treatment of this type of leukemia, which currently has a poor survival rate of 35%, compared to the one of the most common leukemia, which is 80%.

- The aim is to understand glucocorticoid resistance and generate a bispecific CAR-T, which is the most sophisticated therapy and the best ally against leukemia, and which is also changing the way in which medicine fights the disease.

The winning project "Novel and Innovative Therapeutic Strategies for Patients with Childhood B-cell Acute Lymphoblastic Leukemia with MLL Rearrangement" has been selected following the suitability criteria of the State Research Agency of the Spanish Ministry of Science and Innovation.

There are many types of leukemias, but they all have in common the malignant transformation of some of the cells responsible for blood formation. As in most cancers, the transformed cells forget their physiological program and grow out of control causing serious damage.

B-cell acute lymphoblastic leukemia is the most common pediatric cancer. It affects B-lymphocytes, the immune cells responsible for the production of antibodies and which, under normal conditions, protect us from infections. B-ALL patients suffer from recurrent infections, fever, bruising and severe anemia.

Luckily, more than 80% of patients overcome the disease thanks to therapy combining glucocorticoids with other chemotherapeutic agents. And, more recently, in those patients with a poor prognosis that relapse after receiving conventional treatments, they overcome the disease with immunotherapy addressed against the B-cell-specific marker CD19. However, there are subtypes with poor prognosis, as leukemias with MLL alterations which, after apparently successful treatments, very often relapse.

First step: understand the cause of relapse

Dr. Bueno's research group determined in a previous work that the NG2 gene is closely related to these relapses, as it promotes the resistance of leukemic cells to glucocorticoids. This discovery is protected by a European patent, with a view to its therapeutic implementation in the future. 

Second step: development of an immunotherapy, a biospecific CAR-T, thanks to the Unoentrecienmil grant.

Dr. Bueno's working hypothesis is that an immunotherapy addressed against NG2 and the CD22 marker (relapses often present leukemic cells without the standard CD19 marker) should be able to find and eliminate MLLr ALL-B leukemic cells selectively and promote patient improvement. The goal is to develop a biospecific CAR-T against NG2 and CD22 capable of acting in relapsed cases.

A CAR-T is a therapy that consists of genetically modifying the patient's own healthy lymphocytes in the laboratory so that they themselves have the capacity to destroy the cells that they identify as diseased, those that present the NG2 and CD22 markers. CAR-T therapies are the latest and most sophisticated ally against cancer, especially leukemia, and are revolutionizing the way medicine fights the disease.

Elena Huarte-Mendicoa, director of the Unoentrecienmil Foundation highlights the ten years and 15 research projects launched and recognizes that "it is a source of pride to see such promising results. Being part of this movement in the fight against leukemia is not only our goal, but we already feel it as a responsibility. We are sure that, in a few years, thanks to this research and the commitment to immunotherapy, the survival rate of these babies will be much higher. Many lives will be saved”.

Doctor Evarist Feliu, vice-president of the Josep Carreras Foundation and president of the Management Commission of the Josep Carreras Leukaemia Research Institute, attended the award ceremony and expressed his gratitude for the collaboration with the Unoentrecienmil Foundation to advance research and the cure for childhood leukemia.