New STAb cell immunotherapy created for a type of leukemia with few treatment options

Luis Álvarez-Vallina, head of the H12O-CNIO Cancer Immunotherapy Clinical Research Unit. / Laura M. Lombardía. CNIO

• This new therapy, created by researchers at the Hospital 12 de Octubre-CNIO and the Josep Carreras Research Institute, could be used against T-cell acute lymphoblastic leukemia (T-ALL) in those patients for whom chemotherapy or bone marrow transplantation have not worked

• STAb-T therapy is an evolution of CAR-T therapies, one of the recent breakthroughs in the treatment of several types of cancer

• The results are published in the Journal for Immunotherapy of Cancer. Different options are being considered to bring the new therapy to clinical trials

Researchers from the H12O-CNIO Cancer Immunotherapy Clinical Research Unit and the Josep Carreras Leukemia Research Institute, in Barcelona, have developed a cell therapy for a type of leukemia which currently has very few treatment options.

This therapy is based on the use of so-called stab cells, and could be used for the treatment of T-cell acute lymphoblastic leukemia (T-ALL) in those patients for whom chemotherapy or bone marrow transplantation have not worked.

STAb-T therapy is an evolution of the so-called CAR-T therapies, one of the recent breakthroughs in the treatment of several types of cancer.

In CAR-T therapies the patient’s own immune cells -T-lymphocytes- are extracted and modified in the laboratory; once re-injected into the patient, these modified cells will detect and attack the tumor cells. In T-cell acute lymphoblastic leukemia, however, the cells that are used to fight the tumor (T-lymphocytes), are precisely the same type of cells that are diseased.

In STAb-T therapy, the patient’s T cells are modified to produce a special type of antibody that can recognize two targets, one on the tumor cell and one on the T cell. This bispecific antibodies create a kind of artificial bridge that brings therapeutic T cells into contact with tumor cells, facilitating the elimination of the latter and keeping healthy T cells safe.

Towards more personalized therapies

This strategy “could be an improvement over CAR-T, especially in relapsed patients with a reduced number of normal T lymphocytes,” says Luis Álvarez-Vallina, director of the H12O-CNIO Cancer Immunotherapy Clinical Research Unit, and co-author of the study, together with Pablo Menéndez and Diego Sánchez Martínez, from the Josep Carreras Leukemia Research Institute.

“The future in cancer and leukemia research lies in personalized therapies that provide options for all those who find no alternative to conventional therapies; STAb-T therapy is on this path,” adds Álvarez-Vallina.

T-cell acute lymphoblastic leukemia is a rapidly progressive type of leukemia resulting from the abnormal proliferation of T-cell lymphoblasts (immature white blood cells) in the bone marrow and blood. It accounts for about 10-15% of all acute leukemias diagnosed in children and 20-25% of those affecting adults. About a hundred cases of T-cell acute lymphoblastic leukemia are detected each year in Spain.

Expanding the patients who benefit from immunotherapy

The work that explains these results is published in the Journal for Immunotherapy of Cancer. Researchers Anaïs Jiménez-Reinoso and Nestor Tirado, and other members of both teams, have shown that STAb-T cells work very efficiently in the laboratory. Different options are currently being considered to bring this therapy to clinical trials.

Immunotherapy strategies and adoptive cell therapies still benefit few patients. “New strategies are needed that can be directed at specific targets for each disease and adapted for each patient”, explains Dr. Alvarez-Vallina.

It is important to note that STAb-T therapy can be applicable to multiple types of cancer and some of these modalities are in clinical development.

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