SJD Barcelona Children's Hospital launches a platform to produce and develop advanced therapies like CAR-T

The SJD Barcelona Children's Hospital has launched a new platform to produce and develop advanced therapies and medications, such as CAR-T cells, which are used primarily on patients with acute lymphoblastic leukemia who have not responded to conventional treatments. It is also expected to soon be able to produce therapies for other types of cancer—such as diffuse midline glioma—and other diseases.

Until now, specialists at the SJD Barcelona Children's Hospital administered such treatments to patients using therapies produced at other facilities—such as Hospital Clínic Barcelona, thanks to there already being a collaboration agreement between the two—or by pharmaceutical companies. Now the hospital can produce these medications in-house in their own facilities, and will be able to prepare them for patients at other centres.

The new facility is part of the joint immunotherapy platform with Hospital Clínic, coordinated by Dr Manel Juan, and it is already included in the Biocat Advanced Therapies Network of Catalonia, in the Spanish consortiums CERTERA and TERAV—both sponsored by the Carlos III Health Institute—and it is also a member of a European consortium for the production of CAR-T cells in pediatric oncohematology.

Advanced therapies are medications obtained from manipulating genes, cells or tissues in order to treat a disease in an efficient, personalised way. With CAR-T cell therapy in particular, immune cells known as T-lymphocytes are extracted from the patient and genetically engineered to express specific molecules known as Chimeric Antigen Receptors (CAR) on their surfaces. These genetically modified T-lymphocytes are then re-administered to the patient so that their new receptors can detect and destroy cancer cells.

Four cleanrooms

The advanced therapies platform at the SJD Barcelona Children's Hospital spans 1,280 square metres and boasts an advanced therapy production area with four specially designed cleanrooms in which professionals can produce different therapies (using cellular, genetic and tissue engineering). Professionals working in this facility—always within the collaborative partnership between SJD and Clínic—work alongside teams from other departments, such as Oncology, Hematology, Neuromuscular Diseases, Primary Immunodeficiencies and Autoimmune Diseases.

According to Dr Alessandra Magnani, Head of the Advanced Therapies Platform, ‘the creation of this platform was a logical step for our hospital. Here there are clinical experts in extremely complex diseases, researchers who study them and patients who suffer from them and require treatment. Now, with the cleanrooms, we also have the infrastructure to develop and produce these therapies ourselves, and offer new therapeutic opportunities to our patients.’

Some of these therapies already existed, such as CAR-T, indicated for refractory acute lymphoblastic leukemia. We also want to develop different therapeutic strategies in the field of Pediatric Oncology. This is the case, for example, with CAR-T therapy combined with dendritic cell therapy to treat diffuse midline gliomas—a tumour with a very poor prognosis. Or in the field of monogenic diseases, perhaps a new gene therapy for a very rare, severe primary immunodeficiency: MHC class II deficiency syndrome.

In recent years, the SJD Barcelona Children's Hospital has seen a rise in the percentage of patients with rare, complex diseases being attended to, and has launched various initiatives to broaden knowledge of these diseases and to be able to offer new treatments. Of particular note, is the Oncological Hematology team, led by Dr Susana Rives, which was the first in Spain to administer CAR-T therapy to a child with leukemia. It also participated in the development of the Hospital Clínic CAR-T ARI-0001 clinical trial into treatment-resistant acute lymphoblastic leukemia in pediatric patients. Presently, it is coordinating a clinical trial being conducted in five Spanish hospitals about using CAR-T therapy on patients with less advanced disease (first relapse).

A new genre of medications

Advanced therapies include medications that must be produced in very particular facilities that follow strict, specific regulations—Good Manufacturing Practices (GMP)—to ensure that the finished product is of utmost safety for use on patients. Recently, the Spanish Agency of Medicines and Medical Devices (AEMPS) inspected the facilities at the new SJD Advanced Therapies Platform, awarding them with full certification. ‘The positive result of this inspection does not only reinforce the quality and safety of our procedures, but also reinvigorates our mission to offer innovative, effective treatments for cancer’, explains Dr Julio Castaño, Technical Director of the Platform Production Area.

Very few hospitals have these facilities, known as cleanrooms, because they entail a very significant economic investment, as well as specific infrastructure, equipment and expert staff. ‘In our case’, explains Dr Alessandra Magnani, ‘it was the logical next step we needed to take after opening the SJD Pediatric Cancer Center Barcelona—where we attend patients from around the world with extremely complex cancers—and it went hand-in-hand with the launch of the SJD Únicas project for personalised medicine in the treatment of rare diseases.’

Unlike other platforms, the facilities at SJD allow for both the production and development of advanced therapies for the pediatric age group to come together in the one space. ‘Concentrating research, development and production of advanced therapies into the one space is a crucial part of our transversal healthcare goal. It allows us not only to apply our research findings directly to clinical practice, but it also facilitates follow-up of patients who receive the therapies we produce, allowing us to continue building on and improving our treatments. By learning about the whole manufacturing process for an advanced therapy—instead of it arriving pre-made from an external laboratory—we are able to optimise every aspect of its production, discerning why it could have different results from patient to patient, and ultimately, we can offer children more effective, personalised treatments’, explains Magnani.

In the field of research, staff at the SJD Barcelona Children's Hospital and Hospital Clínic who work in the cleanrooms have already begun to research the development of a new gene therapy to treat a very rare, severe form of primary immunodeficiency: MHC class II deficiency syndrome. Children with this disease have no protection against common pathogens that, for most people, are harmless. This leaves them vulnerable to sickness from a very young age. If left untreated, this immunodeficiency can be life-threatening during the first ten to 20 years of life.

The Advanced Therapies Platform—co-financed by the State Network Consortium for the Development of Advanced Therapy Drugs (CERTERA) and by the Ministry of Research and Universities at the Generalitat de Catalunya—would not have been possible without the vital donations of its supporters. In particular, support from Ms Rosalía Gispert, as well as donations from the Bosch Aymerich Foundation and the company Areas, who facilitated the acquisition of equipment needed to develop this infrastructure.