The Research Institute of the Hospital de la Santa Creu i Sant Pau - IIB Sant Pau has developed a new CAR-T immunotherapy drug. As a part of a clinical trial, the drug has just started to be administered to patients with some types of lymphoma (diffuse large cell B lymphoma, follicular lymphoma, mantle cell lymphoma) that have not responded to other treatments. With this new therapeutic proposal, unique in Spain for these patients, Sant Pau offers its second academic advanced therapy drug, which means that it has been produced and developed entirely at Sant Pau. This new CAR-T is characterized by being enriched in Memory T lymphocytes, which are more durable over time, with the aim of having greater efficacy against the disease.

The clinical trial has been promoted, coordinated, and directed from Barcelona by Dr. Javier Briones, Director of the Cellular Immunotherapy and Gene Therapy Research Group at the IIB-Sant Pau, head of the Clinical Hematology Unit of the Hematology Department at the Hospital de Sant Pau and member of the Josep Carreras Leukaemia Research Institute. It also involves the Hematology Department of the Hospital Virgen del Rocío in Seville, within the framework of the Advanced Therapies Network (RICORS).

The Carlos III Health Institute, the Josep Carreras Leukaemia Research Institute and the Blood and Tissue Bank of Catalonia are also collaborating in this project, which has received a grant of 2 million euros from the "la Caixa" Foundation. In the current phase of the trial (Phase I), 10 patients will be recruited, and the objective is to include 30 more in Phase II, with the aim of treating a total of 40 patients over the next two years.

Lymphoma is the most frequent blood cancer in Spain, as stated in the annual report of the Spanish Society of Medical Oncology (SEOM), which estimates that almost 10,000 new cases of non-Hodgkin's lymphoma will be diagnosed in 2023. This is an oncological disease of the lymphatic system that mainly contributes to the formation and activation of the body's defenses. Most patients respond positively to intensive courses of chemotherapy and often to a bone marrow transplant. However, many of these patients relapse after some time and, when this happens, they have very few therapeutic options available to them.

The Sant Pau therapeutic approach addresses more than 80% of all lymphomas. There is currently no approved and marketed CAR-T immunotherapy treatment available in Spain for follicular lymphoma or for mantle cell lymphoma in patients refractory to at least 2-3 conventional treatments.

The advanced therapy drug produced at Sant Pau is based on selecting a specific type of T lymphocytes, called Memory T lymphocytes, which are few but extremely effective. These cells are generated as a defense mechanism of the organism against a primary infection and are responsible for mediating the defense against successive infections of the same pathogen. In other words, they remember the pathogen. In addition, they are known to have a powerful effect against tumor cells.

Dr. Javier Briones, clinical leader of the project, states: "We select these Memory T lymphocytes from the patient himself and train them so that each time they detect a tumor cell, they eliminate it. Thus, in the patient's body there would remain a "detector and eliminator" of any lymphoma cell that might reappear. In short, it is the genetic modification of the patient's own T-lymphocytes so that they attack cancer cells.

Cutting-edge technology to produce advanced therapies

Sant Pau, which is part of the European T2Evolve project, is one of the accredited centers in Spain authorized to use CAR-T drugs by the General Directorate of Basic Portfolio of Services of the National Health System and Pharmacy, which is part of the Ministry of Health, Consumption and Social Welfare. This center has first class facilities, as well as highly qualified and specialized professionals, which enables to develop CAR-T immunotherapy projects that are unique in Europe.

IIB Sant Pau's Clean Room has been certified by the Spanish Agency of Medicines and Health Products (AEMPS) to comply with the Standards of Good Manufacturing Practice for Advanced Therapy Medicines, initially obtained in 2020 in collaboration with the Blood and Tissue Bank of Catalonia, and renewed in 2022, doubling its production capacity.

This equipment has been specially designed for the development of advanced therapy drugs and enables Sant Pau researchers to offer innovative treatments to their patients. In 2020, the first trial was initiated with a CAR-T immunotherapy drug, a pioneer in Europe, for the treatment of relapsed or refractory classical Hodgkin's lymphoma and CD30+ non-Hodgkin's lymphoma T CD30+. The Josep Carreras Leukaemia Foundation and the Josep Carreras Leukaemia Research Institute have strongly collaborated in the project with the acquisition of an important part of the equipment and the provision of funds for the production of drugs for the first 10 patients.

In this sense, the Josep Carreras Leukaemia Research Institute acquired two new cell production units that have been located at Sant Pau. For the purchase of the first one, the Josep Carreras Foundation launched a fundraising campaign in 2018 with the title "The unstoppable cell factory".

The Josep Carreras Foundation has contributed more than 2 million euros to boost the start of this trial.

This study, whose first results were presented last year at the most prestigious international hematology congresses, is currently in phase II and constitutes the first CAR-T30 immunotherapy drug (academic), entirely produced at Sant Pau, which has attracted patients from various countries, such as Italy, Austria, Poland, Russia, among others.

In phase I it was possible to demonstrate that CAR30 memory T cells (HSP-CAR30) have an excellent safety profile, i.e., they have very little toxicity, in addition to achieving high efficacy, since 50% of patients had a complete response to treatment with disappearance of the lymphoma.