The consortium led by the company OneChain Immunotherapeutics (OCI), spin-off of the Josep Carreras Institute (IJC) and Dr. Pablo Menéndez, has received support from the Spanish Ministry of Science, Innovation and Universities to bring an innovative therapy to the clinical phase. This therapy could treat up to 80% of patients with T-cell acute lymphoblastic leukaemia (T-ALL), a rare condition with few therapeutic options, affecting children (60%) and adults. The project, set to last three years, will involve collaboration with the IJC and the Blood and Tissue Bank (Banc de Sang i Teixits).

The treatment of acute lymphoblastic leukaemia type T, one of the most aggressive forms of leukaemia, has historically relied on intensive chemotherapy. Despite improvements in survival rates, this therapy results in devastating effects for patients. Furthermore, a significant percentage of them do not respond to treatment. "For patients who have experienced a relapse, finding effective treatments is particularly challenging," explains Dr. Viìctor M. Diìaz, research director at the company, "our therapy brings hope to these patients".

OCI's approach is based on CAR-T technology, a type of immunotherapy that involves extracting immune cells from the patient to modify them in the laboratory, enhancing their ability to recognize and attack cancer cells and has shown great promise in other forms of leukaemia and lymphoma. "Our aim is to develop this therapy over the three years of the project to initiate a first clinical trial in humans", Dr. Diaz adds.

Attacking the same cell through different targets

The therapy developed by OCI will simultaneously target two markers present on cancer cells, making it more effective than single-target therapies and expanding the number of treatable patients. CAR T therapy has not yet become a consolidated option against T-cell leukaemia, such as T-ALL, because tumour and healthy T cells exhibit almost the same molecules on their surface. As a result, CAR T therapies aimed at T-ALL destroy both types of cells, leading to severe immunosuppression in patients.

OCI has already developed a CAR-T therapy directed at the CD1a protein, a safe target with little presence in healthy cells. However, this molecule is present in cortical T-ALL (coT-ALL), a subset of T-ALL, representing only 30-40% of T-ALL patients. "The first CAR T therapy we developed, targeting the CD1a antigen, is already in clinical trials, demonstrating its safety and efficacy for a specific group of patients," Dr. Diaz explains. "By incorporating a second target into our strategy, we do not only increase the percentage of patients we could treat—up to 80%—but also enhance the effectiveness of the therapy".

The grant has been awarded in the call for public-private collaboration projects by the Spanish Ministry of Science and Innovation. It is the result of recognition awarded to projects that have already reached an advanced phase of development and are ready to transition to clinical application. "We are in a unique position to make a real difference in the lives of patients, expanding our therapies to include those who previously had few options," Dr. Diaz says.

Acute Lymphoblastic Leukaemia Type T: A Rare Disease

Acute lymphoblastic leukaemia (ALL) is a type of cancer affecting the bone marrow, the soft tissue within our bones where blood cells are produced. It is characterized by the excessive production of immature lymphocytes (white blood cells) that do not function properly. These abnormal lymphocytes rapidly multiply, interfering with the production of healthy blood cells and can spread within a few months to different parts of the body, such as the lymphatic system, liver, or spleen.

It is an aggressive and uncommon cancer, with an incidence of around 1.5 cases per 100,000 inhabitants in high-income countries. Depending on the affected cell type, there are two types of ALL, B-cell ALL (ALL-B) and T-cell ALL (ALL-T). The latter, which this new therapy targets, is even rarer, with about 100 cases diagnosed per year in Spain, accounting for approximately 10-15% of all acute leukaemia in children and between 20-25% in adults.

It is a highly heterogeneous disease with many subtypes, which complicates research and the development of effective treatments. Therefore, innovation and the development of targeted therapies are essential to increase treatment options for these patients.