Ignacio Melero
Professor of Immunology at the University of Navarra, CIMA researcher and co-director of the Department of Immunology and Immunotherapy at the Clínica Universidad de Navarra.
This study defines a novel strategy to enhance the anti-tumour effect of CAR-T cells. As is known, CAR-T cells encode for an artificial antigen receptor that recognises surface proteins present selectively or exclusively on tumour cells. In this case, the lymphocytes are transfected with a soluble bispecific antibody that binds to the same tumour antigen and the CD3 receptor to activate themselves and surrounding T cells. It is worth noting that Dr. Alvarez Vallina pioneered the molecular construction strategies that have given rise to CARs when he was working as a postdoctoral scientist at Cambridge University in the late 1990s.
It is a new idea and the effect against malignant cells appears very potent in cell culture and in immunodeficient mice engrafted with human multiple myeloma cells. CAR-Ts are the therapy of choice in myeloma refractory to conventional treatments and these strategies, if confirmed safe and effective in patients, could potentially improve existing ones.
These experimental studies could potentially be extended to other haematological tumours and solid tumours. Currently, extending the efficacy of such therapies beyond haematological malignancies is a challenge of great research interest around the world. There are multiple novel strategies and this work aligns as one of them.
Both CAR-T and bispecific antibody T cell engagers raise issues of acute toxicity in patients with hyperinflammatory cytokine-releasing syndromes. If clinical trials are developed, this aspect should be carefully considered and the production of the bispecific antibody should be regulated so that it is only expressed when it works by recognising the antigen or incorporating other safety measures.