Spanish researchers have announced the development of a new cell-based immunotherapy for multiple myeloma.
The treatment is based on STAb-T cells – engineered T cells secreting T cell engager (TCE) antibodies. The team claim their latest laboratory studies suggest they could be more effective than existing CAR-T treatment.
The scientists say their process is similar to CAR-T, in that T cells are modified to produce an engineered antibody which recognises the BCMA antigen. However, in the case of STAb-T cells, they secrete a bispecific antibody which recruits non-modified T cells to attack malignant plasma cells that over-express BCMA.
Reporting in the journal Science Translational Medicine, the researchers say: “STAb-T cells recruited T cell activity at extremely low effector-to-target ratios and were resistant to inhibition mediated by soluble BCMA released from the cell surface, resulting in enhanced cytotoxic responses and prevention of immune escape of multiple myeloma cells in vitro.”
Their studies show the STAb-T cells are effective again myeloma cells both in experiments in the lab and in mouse models. The researchers say they hope to begin human clinical trials soon.
Researcher Professor Luis Álvarez-Vallina said: “In recent years these cancers have begun to be treated with CAR-T cell immunotherapy, 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.
“We also demonstrated that STAb-T cells generate immunological memory. This is important 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”.
Source:
Díez-Alonso L, Falgas A, Arroyo-Ródenas J, Romencín PA, Martínez A, Gómez-Rosel M, Blanco B, Jiménez-Reinoso A, Mayado A, Pérez-Pons A, Aguilar-Sopeña Ó, Ramírez-Fernández Á, Segura-Tudela A, Perez-Amill L, Tapia-Galisteo A, Domínguez-Alonso C, Rubio-Pérez L, Jara M, Solé F, Hangiu O, Almagro L, Albitre Á, Penela P, Sanz L, Anguita E, Valeri A, García-Ortiz A, Río P, Juan M, Martínez-López J, Roda-Navarro P, Martín-Antonio B, Orfao A, Menéndez P, Bueno C, Álvarez-Vallina L. (2024) “Engineered T cells secreting anti-BCMA T cell engagers control multiple myeloma and promote immune memory in vivo”. Science Translational Medicine, doi: 10.1126/scitranslmed.adg7962
Link: https://www.science.org/doi/10.1126/scitranslmed.adg7962
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