2023-07-21 22:03:04
Fighting cancer and improving care for cancer patients is one of the objectives of the “la Caixa” Foundation, which promotes the development of CAR-T immunotherapies in which the patient becomes their own donor. The Hospital Clínic-IDIBAPS and the Hospital de Sant Pau (IIB-Sant Pau), both in Barcelona, have developed pioneering medicines in Europe to combat lymphoma and multiple myeloma.
by UE Studio
EU STUDY
This content has been developed by UE Studio, a creative branded content and content marketing firm of Unidad Editorial for Fundación ‘La Caixa’.
It is only progress if we all progress. And, in this progress, health plays an important role in which research and innovation are needed. Promoting scientific talent, supporting researchers who work every day to improve the health of all, people who strive to achieve goals as important as curing cancer, preventing Alzheimer’s and cardiovascular diseases or fighting emerging infections is the way to build a better world for everyone. Because today’s research, which is our health tomorrow, can have a great social impact. Hence the importance of promoting advances in biomedicine and health to provide new knowledge and solutions to the fields of the most prevalent diseases —oncological, cardiovascular, infectious and neurodegenerative— with a transversal and interdisciplinary view of social challenges and attention to new technologies.
This is something you already do “la Caixa” Foundation in its commitment to the present and the future of people, focusing on those programs with the greatest transformative impact. Like the development of CAR-T therapies against cancer, a type of cell and gene therapy in which the patient becomes their own donor. They are already beginning to be applied in our country and have opened a new door to the treatment against some types of tumors with promising results, although they pose some challenges, such as their high price. In most cases, they are supplied through a pharmaceutical company, since they are the result of private clinical trials. However, in recent years, academic CAR-Ts are beginning to be created, promoted by the hospitals themselves and with more affordable costs.
What are Car-T cancer therapies?
These innovative therapies consist of modifying T lymphocytes —a type of white blood cell responsible for the anti-infectious and anti-tumor immune response— so that they have the capacity to attack tumor cells. Through apheresis, a technique that allows the separation of blood components, T lymphocytes are obtained, which are genetically reprogrammed so that, when they are reinfused into the patient, they can recognize, attack and destroy cancer cells.
The CAR-T (Chimeric Antigen Receptor T-cell) combines three types of therapy: cell therapy, immunotherapy and gene therapy. It is considered a cell therapy because it is a “living” drug that is infused into the patient. It is also an immunotherapy because the cells of the patient’s immune system are the ones that will fight cancer cells. And, thirdly, it is a gene therapy (one of the first approved by the FDA) because lymphocytes are genetically modified to fight the disease.
Collaborations that give life
Thanks to the strategic alliance signed by Fundación la Caixa” and the Hospital Clínic de Barcelona to promote pioneering research with great impact and healthcare improvement, the first CAR-T in Europe, the ARI-0002h, for the treatment of multiple myeloma, came to light. This collaboration agreement, renewed in July 2023, strengthens the commitment that both institutions have maintained for more than a century to make a qualitative leap in improving the health of sick people and their families. “la Caixa” Foundation will allocate €4.6 million to promote research at the Hospital Clínic Barcelona with the aim of developing new personalized therapies for various types of cancer. And to support two translational research programs that aim to address specific health challenges through collaboration between fundamental, translational, and clinical researchers.
“This is the second CAR-T that we have developed at the hospital. On this occasion, unlike ARI-0001 (for the treatment of acute lymphoblastic leukemia), it is directed against another target, BCMA, the most widespread antigen in myeloma immunotherapy,” explains Dr. Manel Juan, head of the Immunology Service at the Biomedical Diagnostic Center of the Hospital Clínic-IDIBAPS and head of the advanced therapy platform between Hospital Sant Joan de Déu and Hospital Clínic.
“In the future, there will be a significant increase in CAR-T therapies in other hematological cancers, and in cancers in which it is already used, new designs will be created and for earlier stages of the disease.” Javier Briones.
Head of the Clinical Hematology Unit and director of the Cellular Immunotherapy and Gene Therapy Research Group of the Sant Pau Hospital Research Institute (IIB-Sant Pau).
Although there are various treatments for multiple myeloma, from chemotherapy to bone marrow transplantation, there are people who do not respond and therefore have a very limited life expectancy. The results of the CAR-T developed by the Hospital Clínic-IDIBAPS team are very encouraging. A clinical trial has shown that 75% of patients maintain the response after 12 months from the start of treatment.
Another pioneer in the development of CAR-T immunotherapies is Dr. Javier Briones, head of the Clinical Hematology Unit and director of the Cellular Immunotherapy and Gene Therapy Research Group at the Sant Pau Hospital Research Institute (IIB-Sant Pau). Together with his team, he has led the creation of the first CAR-T in Europe for patients with classical Hodgkin lymphoma and T-cell non-Hodgkin lymphoma. According to the Spanish Society of Medical Oncology, this disease affects three out of every 100,000 people.
Doctor Manel Juan, head of the Immunology Service at the Biomedical Diagnostic Center of the Hospital Clínic-IDIBAPS and responsible for the platform of advanced therapies between the Hospital Sant Joan de Déu and the Hospital Clínic.
Research in new therapies
The research group, which also has support from the ”la Caixa” Foundation, has recently developed new CAR-T 19 SP for patients with different types of B-cell non-Hodgkin lymphoma. This new CAR-T immunotherapy drug has just begun to be administered, as part of a clinical trial, to patients with some types of lymphoma (diffuse large B-cell lymphoma, follicular lymphoma, or mantle cell lymphoma) who have not responded to other treatments. With this new therapeutic proposal, unique in Spain, Sant Pau offers its second academic advanced therapy drug, which means that it has been produced and developed entirely in the hospital. This new CAR-T is characterized by being enriched in memory T lymphocytes, more durable over time, with the aim of having greater efficacy against the disease.
“Currently, the vast majority of CAR-T therapies are autologous, that is, they use the patient’s own cells, which is why there is no rejection. CAR-T therapies are now beginning to be carried out with allogeneic lymphocytes, from healthy donors, and in these cases there is a high probability of rejection, but without the clinical implications that we see in patients who receive, for example, a hemopoietic or solid organ transplant”, explains Dr. Javier Briones, clinical manager of the project.
Lymphoma and myeloma, the most frequent
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 lymphoma will be diagnosed by 2023. It is an oncological disease of the lymphatic system that mainly contributes to forming and activating the body’s defenses. Most patients achieve complete elimination of the disease after undergoing intensive courses 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.
Multiple myeloma accounts for 10% of bone marrow cancers and is the second most common blood cancer, behind lymphoma. It is a type of blood cancer located in the bone marrow, where the plasma cells (a type of white blood cells) are in charge of producing the antibodies, necessary to fight infections. In multiple myeloma, plasma cells undergo an abnormal growth process and form tumors in areas of the bone.
The results of the therapies led by Manel Juan and Javier Briones that have been obtained in blood tumors are promising. There are already more than 10,000 patients treated, mainly people who no longer have other therapeutic options. “Due to medical ethics, clinical trials cannot be carried out on patients who have therapeutic options that have previously shown effectiveness. Before carrying out any study, it is necessary to guarantee that they have received the treatments that we know can work”, qualifies Dr. Manel Juan.
After the first cases of success, the current objective is to be able to use these treatments in other non-haematological tumors and they are already being tested in solid tumors such as glioblastoma, sarcoma, breast, ovarian, testicular or gastric cancer.
many questions
How can T lymphocytes be genetically reprogrammed to attack cancer cells? What type of cancer can benefit most from these therapies? What success stories are there already for some tumors? What CAR-T are being investigated in our country? What is the price of these treatments? Could CAR-T therapies be useful for other diseases? Doctors Javier Briones and Manel Juan, specialists in the field, answered all these questions in the CaixaResearch Debate that, on January 31, was organized by Fundación “La Caixa”. It is a cycle of informative debates, aimed at the general public, through which it is intended to give relevance and visibility to the results and new knowledge generated by the projects supported by the institution. They are broadcast in streaming so that the public can follow them live from all over Spain.
This content has been developed by EU Studya creative branded content and content marketing firm from Unidad Editorial for Fundación La Caixa
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