The lab: Fernández de Larrea group

IDIBAPS

Lab's research themes:

The goal is to reduce or eliminate the signs and symptoms of myeloma, amyloidosis, and macroglobulinemia in the long term and even to cure some patients. A strategy for achieving this is manipulation of the patient’s immune system so that it can control the growth of malignant plasma cells.

Only a small proportion of patients with asymptomatic monoclonal gammopathies will develop a malignant gammopathy. Identifying these patients and understanding the mechanisms by which the disease progresses is therefore essential to increasing the efficacy of the treatments and achieving a cure.

Merits of the lab:

Our institution has been and continues to be a pioneer in the development of academic CAR T-cells in Europe. An in-house CAR T-cell designed against CD19 (ARI0001) has shown encouraging results in a phase I clinical trial, and the phase II trial is currently ongoing.

Regarding MM, our group has successfully designed and characterized a CAR against BCMA (ARI0002h), and it is currently in phase I/II of a multicenter clinical trial (NCT04309981; PI: Fernández de Larrea C.) with promising outcomes. Furthermore, our group has already designed a 2nd generation mouse CAR T-cell with encouraging preliminary in vitro results.

Why do we want medical doctors?

We have a long experience training medical doctors. Thus, 6 medical doctors have developed or are developing a PhD in our lab. Some of them have already permanent positions here or at other centers. The PI is also an MD, PhD in a 50/50 program. Our team is diverse in all senses, including now 2 predoctoral and one postdoc being MD.

Country: Spain
Supervisor: Carlos Fernández de Larrea
Fernández de Larrea group

The position

What’s the main purpose of our research?

Despite the available number of treatments for multiple myeloma, the majority of patients end up presenting refractoriness to all available therapeutic lines and some strategies of immunotherapy, such as CAR-T cells, are under evaluation. CAR-T cell therapy is based on the administration of autologous T lymphocytes genetically modified to redirect their specificity against the antigen of interest. The introduction of this therapy in multiple myeloma is being evaluated through the use of CAR-T directed against the BCMA antigen (B-cell maturation antigen), present on the tumor cells. Even with these therapies, many patients will relapse.

How we will do it?

Some questions have emerged when using CAR-T cells in myeloma, such as the role of soluble BCMA, the degree of BCMA expression in plasma cells, its role in the eradication of extramedullary disease or the likelihood of BCMA-negative relapse. In addition, one of the limitations of the use of this therapy is the difficulty to maintain the effectiveness of CAR-T cells over time. Therefore, the possibility of developing a completely new generation of CAR-T is being actively studied. We are working on different strategies to improve the activity, persistence and safety of CAR-T cells for patients with multiple myeloma.

Why is this important?

The goal is to reduce or eliminate the signs and symptoms of myeloma, amyloidosis, and macroglobulinemia in the long term and even to cure some patients. A strategy for achieving this is the manipulation of the patient’s immune system so that it can control the growth of malignant plasma cells. Only a small proportion of patients with asymptomatic monoclonal gammopathies will develop a malignant gammopathy. Identifying these patients and understanding the mechanisms by which the disease progresses is therefore essential to increasing the efficacy of the treatments and achieving a cure.

Who is a good fit for the project?

Basic lab techniques, particularly in immunology and/or hematology, would be very important, as well as statistics and bioinformatics skills.

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