Pan-carcinoma sialyl-Tn-targeting expands CAR therapy to solid tumors
Accurate identification of tumor-specific markers is vital for developing chimeric antigen receptor (CAR)-based therapies. While cell surface antigens are seldom cancer-restricted, their post-translational modifications (PTMs), particularly aberrant carbohydrate structures, offer attractive alternatives. Among these, the sialyl-Tn (STn) antigen stands out for its prevalent presence in various epithelial tumors. Although monoclonal antibodies (mAbs) against STn have been developed, their clinical application has been hindered by concerns regarding specificity. Herein, we describe AM52.1, a mAb with unprecedented specificity for STn and lack of reactivity with healthy tissues. The single-chain variable fragment (scFv) of AM52.1 was assembled into a second-generation CAR scaffold. AM52.1CAR T cells efficiently targeted STn-expressing cancer cell lines and patient-derived organoids (PDOs), while sparing STn-negative cells. In further preclinical models, AM52.1CAR T cells robustly controlled gastric and tubo-ovarian tumors, as well as colorectal cancer mucinous peritoneal metastases, highlighting their strong therapeutic potential for targeting and managing complex solid tumors.
Authors
- Kjersti Flatmark (ORCID: https://orcid.org/0000-0001-7409-0780)
- Emmet McCormack (ORCID: https://orcid.org/0000-0002-7621-4625)
- Rafaela Abrantes (ORCID: https://orcid.org/0000-0002-5441-495X)
- Line Bjørge (ORCID: https://orcid.org/0000-0002-0240-2770)
- Emanuel Senra (ORCID: https://orcid.org/0000-0001-7442-9529)
- Sébastien Wälchli (ORCID: https://orcid.org/0000-0001-5869-1746)
- Catarina Gomes (ORCID: https://orcid.org/0000-0002-0352-6783)
- Ana Filipa Costa (ORCID: https://orcid.org/0000-0003-1691-0482)
- Filipe Pinto (ORCID: https://orcid.org/0000-0001-7634-0296)
- Karianne G. Fleten (ORCID: https://orcid.org/0000-0003-0697-9750)
- Daniela Elena Costea (ORCID: https://orcid.org/0000-0001-7673-0358)
- Puneet Rawat (ORCID: https://orcid.org/0000-0002-3822-8081)
- Klara Krpina
- Rui Henrique (ORCID: https://orcid.org/0000-0003-3171-4666)
- Christopher Forcados (ORCID: https://orcid.org/0009-0003-5073-1522)
- Pascal Gélébart (ORCID: https://orcid.org/0000-0003-2434-8987)
- Ben Davidson (ORCID: https://orcid.org/0000-0003-3332-8427)
- Liliana Santos-Ferreira (ORCID: https://orcid.org/0000-0003-1937-1904)
- Victor Greiff (ORCID: https://orcid.org/0000-0003-2622-5032)
- Celso A. Reis (ORCID: https://orcid.org/0000-0002-0286-6639)
- David J. Warren (ORCID: https://orcid.org/0000-0001-6854-1282)
- Else Marit Inderberg
- Ann Magritt Liberg
Institutions
- Oslo University Hospital (NO)
- University of Oslo (NO)
- Norwegian Cancer Society (NO)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102350
- Citations
- 3
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 3.14