Targeting the Tumour Antigen 5T4 using CAR-T Cells for the Treatment of Acute Myeloid Leukaemia

Abstract Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome deficits in the ability of the host immune system to detect and eradicate tumours. 5T4 is a tumour-associated antigen expressed on the cell surface of most solid tumours. However, very little is known about its expression in haematological malignancies. Herein, we assess the expression of 5T4 in different types of leukaemias, specifically Acute Myeloid Leukaemia (AML), and normal haematopoietic stem cells (HSCs). We also provide an in vitro assessment of safety and efficacy of 5T4-targeting CAR-T cells against HSCs and AML tumour cell lines. 5T4 expression was seen in about 50% of AML cases, specifically AML with mutated NPM1, AML-MR and NOS. 5T4 CAR-T cells efficiently and specifically killed AML tumour cell lines, including the Leukaemic Stem Cells. Co-culture of 5T4 CAR-T cells with HSCs from healthy donors showed no impact on subsequent colony formation, thus confirming the safety profile of 5T4. A murine model for AML demonstrated that CAR-T cells recognise and kill in vivo 5T4-expressing tumour cells. These results highlight 5T4 as a promising target for immune intervention in AML and that CAR-T cells can be considered a powerful personalised therapeutic approach to treat AML.