Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma
Abstract 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+peripher...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-08-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-14572-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849342291412516864 |
|---|---|
| author | Shinsuke Suzuki Xiao-Yan Lin Shuichi Hanada Kimiharu Uozumi Maki Otsuka Satsuki Owatari Koichi Haraguchi Makoto Yoshimitsu Kenji Ishitsuka Hiroshi Takahashi |
| author_facet | Shinsuke Suzuki Xiao-Yan Lin Shuichi Hanada Kimiharu Uozumi Maki Otsuka Satsuki Owatari Koichi Haraguchi Makoto Yoshimitsu Kenji Ishitsuka Hiroshi Takahashi |
| author_sort | Shinsuke Suzuki |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-7b21897ff0bb4deb8cc6cf7bb33dea3b |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-7b21897ff0bb4deb8cc6cf7bb33dea3b2025-08-20T03:43:26ZengNature PortfolioScientific Reports2045-23222025-08-0115111110.1038/s41598-025-14572-1Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphomaShinsuke Suzuki0Xiao-Yan Lin1Shuichi Hanada2Kimiharu Uozumi3Maki Otsuka4Satsuki Owatari5Koichi Haraguchi6Makoto Yoshimitsu7Kenji Ishitsuka8Hiroshi Takahashi9Center for Cancer Advanced Therapy, Kagoshima University HospitalDepartment of Medical Oncology, Fujian Medical University Union HospitalDepartment of Hematology, National Hospital Organization Kagoshima Medical CenterDepartment of Medical Oncology, National Hospital Organization Kagoshima Medical CenterDepartment of Hematology, National Hospital Organization Kagoshima Medical CenterDepartment of Hematology, National Hospital Organization Kagoshima Medical CenterDepartment of Hematology, National Hospital Organization Kagoshima Medical CenterDepartment of Hematology and Rheumatology, Kagoshima University HospitalDepartment of Hematology and Rheumatology, Kagoshima University HospitalVeritas Medical Partners Azabu ClinicAbstract 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.https://doi.org/10.1038/s41598-025-14572-1SF-25 AgSLC3A2HTLV-1Adult T-cell leukemia/lymphomaMagnetic cell sortingc-SF-25 Mab |
| spellingShingle | Shinsuke Suzuki Xiao-Yan Lin Shuichi Hanada Kimiharu Uozumi Maki Otsuka Satsuki Owatari Koichi Haraguchi Makoto Yoshimitsu Kenji Ishitsuka Hiroshi Takahashi Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma Scientific Reports SF-25 Ag SLC3A2 HTLV-1 Adult T-cell leukemia/lymphoma Magnetic cell sorting c-SF-25 Mab |
| title | Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma |
| title_full | Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma |
| title_fullStr | Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma |
| title_full_unstemmed | Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma |
| title_short | Chimeric SF-25 monoclonal antibody as a targeted therapy for SLC3A2 in adult T-cell leukemia/lymphoma |
| title_sort | chimeric sf 25 monoclonal antibody as a targeted therapy for slc3a2 in adult t cell leukemia lymphoma |
| topic | SF-25 Ag SLC3A2 HTLV-1 Adult T-cell leukemia/lymphoma Magnetic cell sorting c-SF-25 Mab |
| url | https://doi.org/10.1038/s41598-025-14572-1 |
| work_keys_str_mv | AT shinsukesuzuki chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT xiaoyanlin chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT shuichihanada chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT kimiharuuozumi chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT makiotsuka chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT satsukiowatari chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT koichiharaguchi chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT makotoyoshimitsu chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT kenjiishitsuka chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma AT hiroshitakahashi chimericsf25monoclonalantibodyasatargetedtherapyforslc3a2inadulttcellleukemialymphoma |