The Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant Pau has developed a new CAR-T 19 immunotherapy drug that has just begun to be administered, as part of a clinical trial, to patients with certain types of lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma) who have not responded to other treatments. With this new and unique therapeutic proposal in Spain for these patients, Sant Pau offers its second academic advanced therapy medicinal product, which means that it has been entirely produced and developed at Sant Pau. This new CAR-T 19 is characterized by being enriched in memory T lymphocytes, which are longer-lasting over time, with the aim of having greater efficacy against the disease.
In the clinical trial, promoted, coordinated, and directed from Barcelona by Dr. Javier Briones, director of the Cellular Immunotherapy and Gene Therapy Research Group of IIB-Sant Pau and head of the Clinical Hematology Unit of the Hematology Service of the Hospital de Sant Pau, the Hematology Service of the Hospital Virgen del Rocío de Sevilla collaborates, within the framework of the Advanced Therapies Network, one of the Cooperative Research Networks Oriented to Health Outcomes (RICORS) promoted by the Carlos III Health Institute (ISCIII).
In this project, which has received a €2 million grant from “la Caixa” Foundation, the ISCIII, the Josep Carreras Leukaemia Research Institute and Banc de Sang i Teixits (Blood and Tissue Bank) also collaborate. In the current phase of the trial (Phase I), 10 patients will be recruited, and the goal is to include 30 more in Phase II, with the aim of treating around 40 patients in total in the next two years.
Lymphoma is the most common blood cancer in Spain, as noted in the Spanish Society of Medical Oncology (SEOM) annual report, which estimates that nearly 10,000 new cases of non-Hodgkin’s lymphomas will be diagnosed in 2023. It is an oncological disease of the lymphatic system that mainly contributes to forming and activating the body’s defenses. Most patients manage to completely eliminate the disease after undergoing intensive cycles of chemotherapy and often a bone marrow transplant. However, many of these patients relapse after a while, and when this happens, they have very few therapeutic options.
Sant Pau’s therapeutic proposal addresses more than 80% of all lymphomas. Currently, there is no approved and commercially available CAR-T immunotherapy treatment in Spain for follicular lymphoma or mantle cell lymphoma in patients refractory to at least 2-3 conventional treatments.
The advanced therapy medicinal product produced at Sant Pau is based on selecting a specific type of T lymphocytes, called memory T lymphocytes, which are few in number but extremely effective. These cells are generated as a defense mechanism of the body against a primary infection and are responsible for mediating defense against successive infections of the same pathogen. That is, they remember it. Furthermore, it is known that they possess a powerful effect against tumor cells.
According to Dr. Javier Briones, the clinical project manager, “We select these memory T lymphocytes from the patient’s own and train them so that every time they detect a tumor cell, they eliminate it. Thus, in a lasting way, there would be a ‘detector and eliminator’ of any lymphoma cell that reappeared in the patient’s body. In short, it is the genetic modification of the patient’s own T lymphocytes so that they attack cancer cells.”
Sant Pau, which is part of the European T2Evolve project, is one of the accredited centers in Spain that has authorization to use CAR-T drugs, granted by the Dirección General de Cartera Básica de Servicios del Sistema Nacional de Salud y Farmacia, which depends on the Ministry of Health. This center has top-level facilities, as well as highly qualified and specialized professionals, which allows them to develop unique CAR-T immunotherapy projects in Europe.
The Clean Room of the IIB Sant Pau has the certification of compliance with Good Manufacturing Practices for Advanced Therapy Medicinal Products, issued by the Spanish Agency of Medicines and Medical Devices (AEMPS), initially obtained in 2020 in collaboration with the Banc de Sang i Teixits (Blood and Tissue Bank), and renewed in 2022, doubling its production capacity.
This equipment has been specially designed for the development of advanced therapy medicinal products and allows Sant Pau researchers to offer innovative treatments to their patients. In 2020, the first trial with a CAR-T immunotherapy drug, a pioneer in Europe, for the treatment of classical Hodgkin lymphoma and CD30+ non-Hodgkin T lymphoma in relapse or refractory, was initiated. 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), totally produced in Sant Pau, which has attracted patients from various countries, such as Italy, Austria, Poland, Russia, among others.
In phase I, it was demonstrated that CAR30 memory T cells (HSP-CAR30) have an excellent safety profile, that is, 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.
