Credit: The Spanish National Cancer Research Centre
Immunotherapy
is already improving treatment options for many cancer types, but research
groups keep exploring ways to boost the body's immune response against the
tumor.
Researchers at 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 shows, in the laboratory, to be
more effective than the immunotherapy currently used as preferred treatment.
The new immunotherapy is based on the so-called STAb
cells. It has yet to pass clinical
trials and therefore it will be at
least two years before it reaches the patients.
The study is published in Science Translational
Medicine, with head of the H12O-CNIO Cancer Immunotherapy Clinical
Research Unit Luis Álvarez-Vallina as senior author. It is a collaboration with
the Josep Carreras Leukemia Research Institute; the Hospital Clínic 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 these cancers have begun to be treated with CAR-T cell immunotherapy," explains Luis Álvarez-Vallina, "which has meant a substantial improvement over previous therapeutic tools. In spite of this, and although patients now have longer survival times, a significant proportion of patients experience relapse, and relapse treatments are needed."
Senior author Luis Álvarez Vallina explains the
findings. Credit: CNIO with graphics by Jesús Sánchez.
Advantages over conventional CAR-T
CAR-T cell therapy (Chimeric antigen receptor T-cell therapy, CAR-T for
short), involves modifying the diseased person's T-lymphocyte immune cells (white
blood cells) in the laboratory so that they acquire the capacity to recognize
and fight tumor cells.
The new study compares this treatment with another cellular immunotherapy
based on STAb-T cells. In both cases, the cells modified in the laboratory
recognize the same antigen, called BCMA, which is only present 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 in that they
recruit natural, non-modified T cells in the body, to 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 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.
BCMA-specific STAb-T cells (red) specifically
recognize and attack myeloma cells (blue). Credit: Anaïs Jiménez-Reinoso
(H12O-CNIO Cancer Immunotherapy Clinical Research Unit) and Manuel Pérez and
Isabel Peset (Confocal Microscopy Unit) / CNIO.
Immunological memory
"Finally, we also demonstrated that STAb-T cells generate
immunological memory," says Álvarez-Vallina. After recapitulating the
disease in animal models and treating them with STAb-T cells, the team obtained
cells from various organs –mainly spleen and bone marrow– and observed
new memory STAb-T cells being produced.
"This is important," explains Álvarez-Vallina, "because the
persistence of CAR-T cells in the body, i.e. immunological memory, is related
to the extent of the antitumor effect and, therefore, to a better control of
the disease. The fact that we have shown that memory cells are also generated
in STAb-T immunotherapy probably indicates that we could have long-term control
of the disease 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.
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