A new treatment based upon bi-specific antibodies may be possible for patients with T-cell acute lymphoblastic leukaemia who have not responded well to previous therapy, researchers have proposed.
Currently, relapsed or refractory T cell acute lymphoblastic leukaemia (T-ALL) is in need of innovative targeted therapies, according to the Spanish researchers.
Therapies based on chimeric antigen receptor (CAR)-engineered T cells are in development, most recently ones that target the protein CD1a on the surface of leukaemic T cells. However, CAR-T cell therapies have some disadvantages for treating T cell leukaemias, compared to B cell malignancies.
So, a Spanish team, from Josep Carreras Institute in Barcelona and Hospital Universitario 12 de Octubre in Madrid, looked at the potential of targeting the CD1a protein in a different way, which they call “STAb therapy”.
The advantage of the STAb therapy over CAR-T therapy is that it is based on the secretion of a special type of antibody that can recognise two targets – one on the tumour cell and one on the T cell – known as a bispecific antibody.
This creates “a kind of artificial bridge that brings therapeutic T cells into contact with tumour cells, facilitating the elimination of the latter and keeping healthy T cells safe”, the researchers report.
In their study, published in the Journal for ImmunoTherapy of Cancer, the team engineered T cells to produce either a CAR or the bi-specific STAb antibody. They then tested these therapies on cells in the lab and in mouse models of cortical T-ALL (a major subgroup of T-ALL). They showed that their STAb therapy is as effective as CAR-T cells in targeting CD1a-expressing cortical T-ALL cells.
They report: “This study validates the efficacy of T cell redirecting strategies targeting CD1a for cortical T cell acute lymphoblastic leukaemia and supports the therapeutic use of CD1a-STAbs as alternative to CD1a-CAR T cells in patients with limited numbers of non-leukemic effector T cells.”
The study was jointly led by Dr Luis Álvarez-Vallina from Hospital Universitario 12 de Octubre, and Dr Pablo Menéndez and Dr Diego Sánchez-Martínez from the Josep Carreras Institute.
Dr Álvarez-Vallina said: “In the case of CAR-T, many hospitals are like a production centre of the therapy. Regarding STAb-T cells, this is a completely new therapy that represents an innovation in the field of cell therapies.”
Jiménez-Reinoso A, Tirado N, Martinez-Moreno A, Díaz VM, García-Peydró M, Hangiu O, Díez-Alonso L, Albitre Á, Penela P, Toribio ML, Menéndez P, Álvarez-Vallina L, Sánchez Martínez D. (2022) “Efficient preclinical treatment of cortical T cell acute lymphoblastic leukemia with T lymphocytes secreting anti-CD1a T cell engagers.” Journal for ImmunoTherapy of Cancer, doi: 10.1136/jitc-2022-005333
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