2020 May 27

CAR-T cells against B-cell Acute Lymphoblastic Leukemia.

Experience of the research project "Innovative therapeutic strategies for mixed-lineage leukaemia: B-cell acute lymphoblastic leukaemia: InTheMLLrBALL", MSCA-IF 795833 by Samanta Romina Zanetti.

Dr. Samanta Romina Zanetti, from the Stem Cell Biology, Developmental Leukemia and Immunotherapy Group of the Josep Carreras Institute, directed by Dr. Pablo Menéndez, has completed the research project associated with the Marie Skłodowska-Curie Action Individual Fellowship (MSCA-IF) grant 795833 "Innovative therapeutic strategies for mixed-lineage leukemia: B-cell acute lymphoblastic leukemia: InTheMLLrBALL".

B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancer in children, and B-ALL with mixed lineage leukemia rearrangement (MLC-r) has a particularly poor prognosis compared to other B-ALL. Many patients with B-ALL are refractory to chemotherapy and eventually relapse. The rationale for launching this project was to develop new CAR-T cell immunotherapy (Chimeric Antigen Receptor T-Cell) for B-ALL patients, both children and adults, who currently have no alternative treatment available.

We talked to Samanta Romina Zanetti about her experience.

Q: What answers were you looking for with your research?

Samanta Romina Zanetti (SRZ): I was looking to develop new immunologically based treatment strategies for patients with B-Cell Acute Lymphoblastic Leukemia, or B-ALL, who are refractory to treatment or in whom the disease returns a few months after treatment (relapse). Currently, promising therapeutic approaches are being developed to combat this type of leukemia, such as patients' T-cell immunotherapy. In this treatment, T cells are modified to express chimeric antigen receptors (CAR) that can bind to the CD19 antigen on the leukemia cells and thus attack and destroy them. Besides, the same strategy has also been tested to target another molecule expressed by leukemia cells called CD22. This type of therapy has shown impressive efficacy, although relapses are frequent. Many patients who relapse lose the expression of CD19 or CD22, making it difficult to find the next therapy that successfully eliminates the remaining leukemia cells.

Q: What progress have you made with your research?

SRZ: As part of this grant, we generated T cells that express a CAR molecule that can recognize both CD19 and CD22 antigen (CD22/CD19-CAR) on leukemia cells and thus hope to prevent relapses by using both antigens as therapeutic targets. Also, we have found an additional molecule that promises to be a new therapeutic target for patients with B-ALL.

Q: From a more personal research perspective, what has the MSCA grant allowed you to do?

SRZ: The MSCA fellowship has opened many doors for me by allowing me to participate in international conferences, courses, and workshops, and to share results with group leaders from Dr. Pablo Menendez's professional network. It has also allowed me to meet other MSCA Fellows, expand my network, and make new friends. Finally, it has allowed me to be the inventor of a patent filed in the EU in March 2020, together with other researchers of the group led by Dr. Menéndez.

Q: Will you continue in the line of research of the project you started thanks to this grant? What social and scientific impact do you think your results could have in this area?

SRZ: Yes, I plan to deepen studies related to the molecule we have found as a candidate for future use in therapy for patients with B-ALL. We need to continue research to understand the functions of this protein in this type of leukemia, and thus improve the effectiveness of current therapies for these patients. Concerning the impact of the results obtained during this grant, not only do we generate new knowledge about the disease, but they are also crucial for society. In particular, for patients with B-ALL who currently have no alternative treatment, given that the results obtained provide essential information for launching a clinical trial with CD22/CD19-CAR in the future.