Clinical trial in Zaragoza: a live cancer drug will be manufactured in a special room at the Servet Hospital for a single patient

A new CAR-T therapy for rare cancers, developed by researchers in Aragon, reprograms each person's immune cells to attack the tumor.

The development of CAR-T19 therapy, which targets the CD19 protein for the treatment of B-cell leukemias and lymphomas, marked a milestone in hematological cancers. Before its advent, the median survival for these patients was only 6–12 months, and long-term survival was less than 10%. With CAR-T19, response rates of up to 90% and five-year survival rates approaching 50% are achieved. This advance, based on reprogram the patient's own immune cells to recognize and destroy the tumorIt opened the door to a new generation of advanced cell therapies and an opportunity to translate research results to patients more quickly.

Since their initial approvals in 2017 in the United States and in 2018 in Europe, CAR-T cell therapies have expanded their indications to include diseases such as multiple myeloma and are beginning to show promising results in autoimmune disorders. However, The high cost of this drug poses a technical challenge for the sustainability of the healthcare system and morally to not refuse to treat any patient who could benefit from this therapy.

La CAR-T manufacturing in hospitals This represents a key strategy for overcoming this challenge. So-called 'cleanrooms' or advanced therapy units allow these therapies to be produced under sterile and controlled conditions, guaranteeing product safety and quality. This model not only facilitates clinical research but also allows already approved CAR-T therapies for hospital use to be produced within hospitals themselves, significantly reducing the cost to the healthcare system—up to 70% compared to industrial manufacturing—and ensuring that more patients have access to treatments quickly and equitably. Spain has been a pioneer in this model, and many autonomous communities now have cleanrooms for producing hospital-use CAR-T therapies.

First real use

In Aragon, it has recently been built at the Miguel Servet University Hospital in Zaragoza. a new advanced therapies unit Thanks to the donation from Clementa Soria through the Spanish Association Against Cancer (AECC).

Currently, the facility is being prepared for its first real use in generating a CAR-T. an essential step for its accreditation before the Spanish Agency for Medicines (AEMPS) and to be able to produce CAR-T therapies for healthcare use in the future.

A multidisciplinary team from the University of Zaragoza, the Aragon Health Research Institute (IIS Aragón), the Lozano Blesa and Miguel Servet Clinical Hospitals, the Aragon Agency for Research and Development Foundation (Araid), the Spanish Network of Advanced Therapies (Terav), and the Biomedical Research Network Center for Infectious Diseases (Ciberinfec) has developed A new CAR-T therapy for myeloproliferative syndromes, rare cancers with no curative options in many casesAfter demonstrating its effectiveness in preclinical models, it is being prepared for production in the new cleanroom and its evaluation in a phase I clinical trial.

This trial will be key not only to validate the safety and efficacy of the treatment in patients, but also for the accreditation of the facility. an essential step to be able to manufacture CAR-T drugs for clinical use and ensure broad and sustainable access.

La joint involvement The involvement of researchers, specialists in production and management of wards, doctors and political managers, who facilitate its sustainability, will be fundamental to the success of the project and its future impact on patients in our community and on the Aragonese health system.

In detail

• Objective Conduct a phase I clinical trial to evaluate a new CAR-T produced at IISA against rare hematological cancers with mutated calreticulin.
• ​Participants Clinical Hospitals Lozano Blesa and Miguel Servet and the Immunotherapy, Cytotoxicity, Inflammation and Cancer group (IISA/Unizar).
• ​Finance Thanks to the posthumous donation of Doña Clementa Soria channeled through the AECC, the clean room has been built and equipped, all the preclinical trials for the development of the CAR T-cell therapy have been carried out, and the documentation for the authorization of the clinical trial has been prepared.
• The fact The trial in patients with myeloproliferative cancer will accredit the cleanroom, benefiting these patients and allowing the application of approved CAR-T therapies in the future through hospital exemption, with annual savings of at least 5 million euros for Aragon.

How to use our defenses against an incurable cancer

Everyday The immune system protects us against infections and tumors, although it sometimes failsSome mutated cells hide, escaping control, and grow uncontrollably, leading to cancer. This occurs in myeloproliferative syndromes, a group of rare blood cancers, such as polycythemia vera, essential thrombocythemia, and myelofibrosis.

Although few new cases are diagnosed each year, its chronic progression means that many patients live with the disease for years, increasing its impact. Currently They have no cureThis reinforces the need for new therapies.

In some of these patients, the tumor cells present mutations in calreticulin, a key protein whose altered version promotes tumor growth. Furthermore, it acts as a distinctive signal that allows cancer cells to be differentiated from healthy cells. CAR-T therapies take advantage of this difference.

Its about extract T lymphocytes from the patient and genetically modify them so that, taking advantage of their natural ability to destroy tumors, they recognize and destroy tumor cells.

Thus, the patient's own immune system, once extracted, is modified in the laboratory to become a living, personalized medicine, which is then administered back to the patient so that it can finally find and eliminate cancer cells without harming healthy tissue. We have developed a new CAR-T therapy targeting mutated calreticulin in myelofibrosis and essential thrombocythemia, allowing to selectively eliminate tumor cells without damaging healthy tissues.

Why is it possible to manufacture CAR-T therapies within the hospital?

Traditionally, medicines are composed of synthetic, natural, or biological substances that act when administered within the patient. They are produced in pharmaceutical factories They are then sent to hospital pharmacies or public pharmacies, where they can be stored until needed. They can be administered to multiple patients with the same illness, making their manufacture and application more sustainable. 

In personalized therapies such as CAR-T, The patient's own cells are used to manufacture their medicine, which cannot be used in another patient, thus increasing its cost.Since the patient's own cells become the "factory" of the drug and each treatment is unique, CAR-T cells can be produced in smaller, safer facilities within the hospital itself, close to the patient. This reduces costs and makes its application more sustainable, allowing more patients to receive it. This is called outpatient treatment and represents the future of these therapies, combining industrial and hospital production.

How can we make life-saving therapies manufactured close to the patient?

The production of CAR-T cells from the patient's own cells, It requires highly controlled environments called 'clean rooms'In these facilities, temperature, humidity, airborne particles, and the presence of potential toxins and infectious agents are rigorously monitored. Teams of specialists with expertise in cell production, pharmaceutical regulations, efficacy and safety evaluation, and strict quality controls work in these spaces, ensuring that every medication produced is safe for the patient. 

Although these facilities require sustained investment, Producing CAR-T for two or three patients a year represents a saving that practically covers the annual cost of the operating room.making the investment efficient and profitable, as well as providing a direct benefit to patient survival. 

Thanks to these facilities, Production can be done directly in the hospitalThis ensures that therapy reaches patients more directly and quickly without the need to travel to other centers, thus avoiding travel-related difficulties. Furthermore, in the long term, CAR-T therapies can be more cost-effective as they are single-administration treatments with curative potential compared to prolonged chronic therapies.

Source: Heraldo de Aragón