World’s first clinical trial with CAR-T technology for patients with T-cell leukemia subtype authorized

The Spanish Agency of Medicines and Medical Products (AEMPS) has approved the CARxALL clinical trial led by the company OneChain Immunotherapeutics (OCI). It will be the world’s first trial with CAR-T technology for patients with a subtype of T-cell leukemia.

The CARxALL trial will evaluate, for the first time, the CAR-T CD1a (OC-1) therapy. This treatment specifically targets a subtype of T-cell leukemia, cortical T-cell acute lymphoblastic leukemia (coT-ALL), which accounts for 30-40% of T-ALLs and has a poor prognosis in patients who do not respond to currently available treatments.

The clinical production of the CD1a CAR-T therapy for the trial has been led by Dr. Maria Castellà, a doctor in the Immunology Service at the Biomedical Diagnostic Centre of Hospital Clínic Barcelona, directed by Dr. Manel Juan.

The trial will be conducted at Hospital Clínic and Hospital Sant Joan de Déu in Barcelona, under the direction of Dr. Núria Martínez and Dr. Susana Rives, principal investigators for the study.

It is expected to include both pediatric and adult patients without any therapeutic alternatives. Although the patients will be treated in Barcelona, patients from Spain and across Europe may join the trial.

The group led by Dr. Menéndez, founder of OCI and director of the Josep Carreras Institute’s stem cell biology, developmental leukemia and immunotherapy group, was the first in the world to develop and validate a CD1a-specific CAR-T for coT-ALL. The study, led by Dr. Diego Sánchez and published in the journals Blood and the Journal for ImmunoTherapy of Cancer, has been conducted with animal models using cell lines derived from patients with coT-ALL. Preliminary results show that these CAR-T cells persist in vivo in the long term and retain their anti-leukemia activity.

The CARxALL clinical trial represents another step towards developing adoptive cell immunotherapy, such as CAR–T cell therapy, a treatment that consists of extracting a patient’s T cells (cells that protect the body from infection), modifying them in the laboratory and returning them to the patient. This modification enables the cells to attack and eliminate the receptors located in the membranes of tumor cells. With this technique, the patient’s own modified cells attack the cancer cells in a directed way, without damaging healthy cells.

OCI achieved this important milestone after being created in 2020 through a round of seed capital amounting to 3.05 million euros provided by Invivo Ventures, CDTI-Innvierte and the Josep Carreras Foundation, and after receiving funding from the State Research Agency. This is a successful case of technology transfer and public-private collaboration involving recovery of public investment in research.

According to Dr. Menéndez, “Developing these strategies and managing all the regulatory mechanisms associated with developing a product is extremely complicated in the academic field. Therefore, OCI will enable us to carry out all the necessary steps to ensure that our knowledge benefits patients”.

Antoni García Prat, the administrator of the Josep Carreras Foundation, added, “The Foundation decided to support the initial investment by Invivo Ventures and CDTI as an indication of its support for translational research and the research team. It is important to keep in mind that the projects concern rare or childhood hematological tumors, or those with few therapeutic alternatives, and that any profits generated for the Foundation will be fully invested in the fight against leukemia, always in the best interests of patients”.

Prof. Evarist Feliu, president of the Josep Carreras Leukaemia Research Institute’s Delegate Committee, said, “Immunotherapy currently constitutes an important field for cancer treatment. Its main clinical relevance currently lies in immune system checkpoint inhibitors and adoptive therapy strategies with T cells, with more than 700 clinical trials taking place throughout the world for the treatment of malignant blood diseases and, to a lesser extent, solid tumors”.

Dr. Lluís Pareras and Albert Ferrer, founding partners of Invivo Ventures, went on to say, “OneChain is developing several programs in the field CAR-T stemming from technology transfer. With its first program, OCI has demonstrated its ability to bring a product based on academic research results to clinical trial in as little as two years. In addition, it has a new allogeneic platform, a hematological tumor program and a solid tumor program in the pipeline”.