New immunotherapy for multiple myeloma proves more effective in the laboratory than already used CAR-T treatment

Immunotherapy is already improving treatment options for many types of cancer, but research groups continue to explore ways to strengthen the body’s immune response against the tumor.

Researchers from the Spanish National Cancer Research Center (CNIO) and the 12 de Octubre University Hospital in Madrid have developed a new immunotherapy to treat multiple myeloma that proves, in the laboratory, to be more effective than currently used immunotherapy as preferred treatment.

The new immunotherapy is based on so-called STAb cells. It has not yet passed clinical trials, so it will take at least two years before it reaches patients.

The study is published in Scientific translational medicine, with the head of the H12O-CNIO Cancer Immunotherapy Clinical Research Unit, Luis Álvarez-Vallina, as lead author. This is a collaboration with the Josep Carreras Leukemia Research Institute; the Clinical Hospital of Barcelona; the University of Salamanca and the Complutense University of Madrid.

Multiple myeloma is the second most common hematological cancer in adults, just after lymphomas. “In recent years, we have started to treat these cancers with CAR-T cell immunotherapy,” explains Luis Álvarez-Vallina, “which represents a substantial improvement compared to previous therapeutic tools. Despite this, and even if patients now have a longer survival time, a significant proportion of patients experience relapse and treatments for relapse are necessary.

Advantages over conventional CAR-T

CAR-T cell therapy (Chimeric antigen receptor T-cell Therapy, CAR-T for short), consists of modifying in the laboratory the immune cells of the T lymphocytes (white blood cells) of the sick person so that they acquire the ability to recognize and fight the tumor. cells.

The new study compares this treatment to another cellular immunotherapy based on STAb-T cells. In both cases, the laboratory-modified cells recognize the same antigen, called BCMA, present only in tumor cells. In this way, the modified cells target and attack only cancer cells.

The results show that STAb-T cells outperform CAR-T cells as they recruit natural, unmodified T cells in the body to also fight cancer cells, thus amplifying the effect of the therapy.

Additionally, STAb-Ts overcome something that slows down CAR-Ts. In some patients with multiple myeloma, the BCMA antigen – which identifies tumor cells – is found in soluble form when there is a high tumor burden. The fact that the antigen is soluble hinders the activity of CAR-T cells but does not affect STAb-T cells, the new result shows.

Immunological memory

“Finally, we also demonstrated that STAb-T cells generate immunological memory,” explains Álvarez-Vallina. After recapitulating the disease in animal models and treating them with STAb-T cells, the team obtained cells from various organs – primarily the spleen and bone marrow – and observed the production of new STAb-T cells. memory.

“This is important,” explains Álvarez-Vallina, “because the persistence of CAR-T cells in the body, that is, immunological memory, is linked to the magnitude of the antitumor effect and, therefore, to better disease control. The fact that we showed that memory cells are also generated in STAb-T immunotherapy probably indicates that we could have long-term disease control in treated patients.

The research group aims to conduct a clinical trial with the 12 de Octubre University Hospital, in Madrid, to treat patients with this new STAb-T immunotherapy.