Multidisciplinary group of the TILs Project.
In recent years, much progress has been made in the research of new therapies that use the capacities of our immune system to fight against cancer. This is what is known as immunotherapy. Within this area there are different strategies such as the development of advanced therapy (ATMP), of which therapy with TIL cells (from the English Tumour-infiltrating Lymphocytes) is a clear example. Now him Vall d’Hebron Hospital has reported the treatment of the first patient with its own cell therapy based on TIL cells, fully developed at the Vall d’Hebron Institute of Oncology (VHIO) thanks to the support of the CAIMI Program of the BBVA Foundation, the Carlos III Health Institute (ISCIII ) and the support of the Banc de Sang i Teixits (BST). In this way, Vall d’Hebron joins the great hospitals in the world capable of developing their own or academic advanced therapy drugs (ATMP) to administer to their patients.
These are lymphocytes – immune cells found mainly in the blood – that penetrate the tumor and, once reactivated in the laboratory, are capable of recognize tumor cells and destroy them. Despite the fact that these lymphocytes are found in the tumor, on many occasions they are not very active or there are few, which does not allow the tumor cells to be eliminated effectively, and, as a consequence, the tumors continue to grow. For this reason, it is essential to reactivate and recover the functionality of the lymphocytes and expand them ex vivo in the laboratory and then re-administer them to the patient.
The team of Alena Groshead of the VHIO Immunotherapy and Immunology Group, who has led the preclinical development of this therapy thanks to the support of the Comprehensive Immunotherapy and Immunology Program (CAIMI) promoted by the BBVA Foundation, has spent years researching
antitumor responses produced naturally by T cells against mutations that occur in different types of tumors, including endometrial cancers and other unresectable epithelial tumors. “Ultimately, it is about creating an army of cells from the patient himself that helps us attack the tumor more effectively,” he explains. Elena Garraldadirector of the Cancer Molecular Therapy Research Unit (UITM) – CaixaResearch.
Due to the characteristics of the immune system, the preparation of this treatment is carried out in a personalized way, for each patient, and at least a month and a half passes from the time the tumor biopsy is obtained, from which the TIL of the candidate patient is obtained. until he receives his treatment. “It is the time it takes to be able to expand a sufficient amount in the laboratory to be able to administer them back to the patient. During this period, the patient continues with his usual treatment and when he stops responding, that is when we infuse the previously prepared TIL cells”, adds Elena Garralda, who also explains that before inoculation it is The patient must undergo a high-dose chemotherapy treatment that destroys the lymphocytes that he already has, to make room for the new TIL cells.
An innovative cell therapy developed entirely in VHIO
Once the TIL cells are infused, patients receive various doses of interleukin-2 (IL-2), which helps expand and activate these cells. This treatment generates adverse effects ‒high toxicity‒ in the short term, which is why it is administered in the Advanced Therapies in Hematology Unit (UTAH) of the Hospital Universitari Vall d’Hebron. It is a specialized and pioneering unit in our country, which allows the administration of cell therapy treatments with semi-intensive care and from a multidisciplinary perspective, in which professionals from different disciplines cooperate to offer the best quality of care to these patients. .
“It is the first step on a path that we know will be long because we are aware that not all patients will respond to this therapybut we hope that it can offer us a new way forward in the personalized cancer mediciner”, explains Alena Gros. “After so many years of work, it is a source of pride both for me and for the entire multidisciplinary team involved in this research project, to be able to evaluate an experimental therapy in patients that has been entirely developed in the laboratory, at VHIO”, he adds, highlighting that, although there are other industry-developed TIL assaysin this case it is an investigation carried out from the academic field, which is a clear case of success.
In Spain there are also cases of patients treated with TIL therapy, with commercial products in clinical trials, but in some cases also with academic products, especially in pediatric indications. Now the Hospital Universitari Vall d’Hebron has also joined this list of leading hospitals capable of offering this experimental therapy for patients with solid tumors who do not have any therapeutic alternative. “This is a state-of-the-art therapy in immuno-oncology, which requires the participation of highly qualified professionals from different fields. Teamwork, coordination and the support of the different units are essential for a project of these characteristics, a pioneer in its kind in Spain, to come out
forward”, comments Silvia Martín Lluesma, Clinical Senior Manager in Advanced Therapies at VHIO (Scientific Coordination Area) and professor at the San Pablo CEU University.
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