Laura Mondragon Martinez, PhD
Junior Group Leader, Cancer and Leukemia Epigenetics and Biology Program
Josep Carreras Leukaemia Research Institute
Research project
New Therapeutic Approach for Treating Angioimmunoblastic T-Cell Lymphoma Based on the Discovery of a New Tfh Population
Summary
Angioimmunoblastic T-cell lymphoma (AITL) is a type of blood cancer affecting mature individuals. It does not present symptoms until the late stages of the disease, when it is usually diagnosed. As a consequence, patient survival does not exceed 32% after 5 years. Its origin lies in a type of T-cell called T follicular helper (Tfh). Tfh activate B cells to initiate the immune response when they detect the presence of infectious agents. Their function ends once this threat has been neutralised, at which point they stop stimulating B cells. However, for unknown reasons, in AITL, Tfh do not stop activating B cells even when the external threat has been neutralised. As a consequence, there is an increase in the number of T and B cells leading to the onset of the disease. To date, there is no specific therapy for its treatment, which greatly reduces the patient's chances of survival. In this project, we propose a new specific therapy from the study of the Apaf-1 heterozygous KO mouse model which mimicks AITL disease as we have observed the presence of a new type of follicular helper T cells that we believe are the true origin of the disease. Thus, we propose in this project to test a new therapy based on the use of antibodies that neutralise and destroy these defective T cells in order to stop this massive division of T and B cells and cure the patient. This therapy will be tested both in animals and in samples from AITL patients.
Impact
The funding received has helped me to start proving a research hypothesis already established in 2016 and, the fact that this hypothesis has been validated during this project constitutes one of the most satisfying achievements in my whole research career. Besides, the results obtained have the potential to open new ways of approaching the study of such a complex disease and to provide new therapeutic strategies much more specific and, most importantly, with no potential secondary effects.
We deeply confide in our research hypothesis and its potential application into clinics, taking into account the results obtained thanks to the Leukemia Research Foundation's help. We will for sure continue in our research till we manage to find a proper therapy and potential cure for AITL, but we will never forget and stop thanking all the people at the Leukemia Research Foundation who made this possible and helped us in our first years as a research group.

Leukemia Research Foundation grant
$100K awarded in 2022
Disease focus
Lymphoma (non-Hodgkin)
Research focus
Treatment (immunotherapy)