The role of chimeric antigen receptor T cells targeting more than one antigen in the treatment of B-cell malignancies.
Helena BrillembourgNúria Martínez-CibriánMireia BachillerLeticia AlserawanValentín Ortiz-MaldonadoSònia GuedanJulio DelgadoPublished in: British journal of haematology (2024)
Several products containing chimeric antigen receptor T cells targeting CD19 (CART19) have been approved for the treatment of patients with relapsed/refractory non-Hodgkin's lymphoma (NHL) and acute lymphoblastic leukaemia (ALL). Despite very impressive response rates, a significant percentage of patients experience disease relapse and die of progressive disease. A major cause of CART19 failure is loss or downregulation of CD19 expression in tumour cells, which has prompted a myriad of novel strategies aimed at targeting more than one antigen (e.g. CD19 and CD20 or CD22). Dual targeting can the accomplished through co-administration of two separate products, co-transduction with two different vectors, bicistronic cassettes or tandem receptors. In this manuscript, we review the pros and cons of each strategy and the clinical results obtained so far.
Keyphrases
- cancer therapy
- nk cells
- end stage renal disease
- multiple sclerosis
- acute lymphoblastic leukemia
- chronic kidney disease
- acute myeloid leukemia
- poor prognosis
- induced apoptosis
- ejection fraction
- cell proliferation
- newly diagnosed
- liver failure
- combination therapy
- oxidative stress
- intensive care unit
- hepatitis b virus
- free survival
- respiratory failure