Stem cell biology, developmental leukemia and immunotherapy

Pablo Menéndez

Introduction
Our Research
Our Goals
Our Challenges
Team
Publications
Current Grants

Introduction

Our group is interested in understanding the cellular origin, etiology and pathogenesis of childhood leukemia. We aim to ascertain the cell in which mutations occur and we strive to discover which cells are responsible for triggering relapses. Furthermore, we work to identify new therapeutic targets and develop more targeted, less toxic therapies. To achieve this, our laboratory uses various approaches, including genetic studies, epigenetic techniques and animal models, as well as adoptive cell immunotherapy tools.

Our Research

Given that acute childhood leukemia (including the B, T and myeloid variants), and childhood cancer in general, are relatively uncommon illnesses, with around 500 cases in Spain each year, it does not represent a priority target for the pharmaceutical industry. As a result, there is a serious lack of active programs that aim to identify medicines to target childhood cancer. Our group has been investigating the origin of this diseases in utero, as well as its etiological causes and physiopathological mechanisms. In 2016, we began researching non-toxic, targeted adoptive cellular immunotherapies for these children with the aim of preventing the long-term effects of current chemotherapy.

Our Goals

Our group is currently involved in various lines of research in pursuit of the following objectives:

To understand the aetiology and pathogenesis of leukaemia in breastfeeding infants. To do so, we use primary samples taken from patients and develop different animal and cellular models based on prenatal (embryonic, foetal) and postnatal (neonatal and adult) stem cells.
To gain a better understanding of the role of bone marrow (BM) stroma in chemoresistance in acute myeloid leukaemia (AML) and identify new therapeutic targets for AML, which is the most common form of leukaemia in adults and whose prevalence increases with age.
To improve adoptive cellular immunotherapies against ALL-B, ALL-T and AML. To achieve this, we are searching for new therapeutic targets and developing new CARs (chimeric antigen receptors) for the different types of acute leukaemia.
Develop therapeutical options for B-ALL with aneuploidy. Understand how aneuploidy and chromosome instability develop in hematopoietic stem and progenitor cells and contribute to leukemogenesis. Project coordinated by Dr. Oscar Molina.

Our overall goal is to contribute towards curing 100% of childhood leukaemias or convert them into chronic conditions, without generating lifelong toxicities.

Our Challenges

Childhood diseases have an enormous emotional impact on the patient’s whole family and everybody around them. Moreover, we must not forget that children are the future of our society, so investing in their health will benefit the future of our society enormously. Through our research, we aim to:

Identify the cellular origin, cellular and molecular mechanisms, and the genetic and epigenetic composition of ALL-B in breastfeeding infants.
Contribute to the development of new therapeutic strategies in AML targeted towards reducing the resistance mediated through the BM microenvironment and that are particularly effective against LICs.
Develop adoptive cellular immunotherapies against ALL-B, ALL-T and AML using allogeneic T-cells without genome editing to eliminate TCR, CD3 and other molecules that play a role in immunological synapse.