Immunotherapy is already improving treatment options for many cancers, but research groups continue to explore ways to boost the body's immune system and use it against the tumour.

Researchers at the Josep Carreras Leukaemia Research Institute, the Spanish National Cancer Research Centre (CNIO) and the University Hospital 12 de Octubre have developed a new immunotherapy for multiple myeloma that has proved to be more effective in the laboratory than the current preferred immunotherapy.

The new immunotherapy is based on so-called STAb cells. It has been tested only in experimental models, so it has yet to pass clinical trials in humans and will therefore take at least two years before it reaches the clinic.

The study, published in the journal Science Translational Medicine, involved Dr Clara Bueno and Dr Aida Falgas, from the Stem Cell Biology, Developmental Leukaemia and Immunotherapy group, and was coordinated by Dr Luis Álvarez-Vallina, head of the H12O-CNIO Cancer Immunotherapy Clinical Research Unit. It is a collaboration between this unit and the Josep Carreras Institute; the Hospital Clínic in Barcelona; and the Universities of Salamanca and Complutense of Madrid.

STAb cells

Multiple myeloma is the second most common haematological cancer in adults, after lymphomas. In 2020, 176,404 new cases of multiple myeloma were diagnosed worldwide and its incidence is estimated at 1.78 per 100,000 people.

In recent years, these cancers are beginning to be treated with CAR-T cell immunotherapy," explains Luis Álvarez-Vallina, "which has been a substantial improvement over the therapeutic tools that existed before. Despite this, and although patients now have longer survival times, it is a disease in which a significant proportion of patients relapse, so relapse treatments are necessary.

Advantages over conventional CAR-T

CAR-T cell therapy, whose full name is chimeric antigen receptor T-cell therapy, involves modifying a patient’s T-cell immune cells (white blood cells) in the laboratory so that they are able to recognise and fight tumour cells.

Research has compared this treatment with another cellular immunotherapy based on or STAb-T cells, which can be considered an evolution of CAR-T cell therapies. In both cases, the laboratory-modified cells recognise the same antigen, called BCMA, which is only present on tumour cells. In this way, the modified cells target and attack only cancer cells.

The study now presented in Science Translational Medicine shows that STAb-T cells outperform CAR-T cells, because they can make other T cells in the body, which have not been modified, also fight cancer cells, thus amplifying the effect of the therapy.

In addition, STAb-Ts overcome an element that slows down CAR-Ts. In some patients with multiple myeloma, the BCMA antigen - which identifies tumour cells - is found in soluble form when there is a high tumour burden. It turns out that the fact that the antigen is soluble prevents the activity of CAR-T cells, but does not affect STAb-T cells, the now-published research shows.

Immune memory

"Finally, we also showed that STAb-T cells generate immunological memory", says Álvarez-Vallina. After recreating the disease in model animals and treating them with STAb-T cells, the team obtained cells from various organs, mainly spleen and bone marrow, and observed the generation of memory STAb-T cells.

“This is very important", explains Álvarez-Vallina, "because we know that the persistence of CAR-T cells in the body, i.e. immunological memory, is related to the extent of the anti-tumour effect and, therefore, to better control of the disease. The fact that we have shown that STAb-T immunotherapy also generates memory cells probably indicates that we could have long-term disease control in treated patients.