Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma

The SF-25 antigen (SF-25 Ag), which functions as the amino acid transporter solute carrier family 3 member 2 (SLC3A2), is essential for regulatory T (Treg) cell maintenance and is highly expressed in adult T-cell leukemia/lymphoma (ATL) cells. We analyzed SF-25 Ag expression in CD4+peripheral blood lymphocytes (PBLs) from 28 ATL patients, 52 healthy human T-lymphotropic virus 1 (HTLV-1) carriers, and eight non-infected individuals. Inverse polymerase chain reaction was used to detect monoclonal integration of HTLV-1 proviral DNA. The median (interquartile range) percentages of SF-25 Ag-positive PBLs in acute, chronic, and smoldering ATL were 54.9% (23.9-62.9), 34.9% (23.8-41.9), and 22.1% (8.4-28.5), respectively, which were significantly higher than those in HTLV-1 carriers (0.8% [0.5-1.0]) and non-infected subjects (0.4% [0.3-0.4]) (P < 0.001). Magnetic sorting isolated SF-25 Ag-positive cells, which showed monoclonal HTLV-1 integration, unlike SF-25 Ag-negative cells. Moreover, culture supernatant from healthy donor PBLs stimulated with a murine-human chimeric SF-25 monoclonal antibody (c-SF-25 Mab) induced apoptosis in SF-25 Ag-positive ATL cells. These findings suggest that c-SF-25 Mab, by targeting SLC3A2, may offer a specific therapeutic approach for ATL by eliminating malignant cells while sparing normal tissue.