biostudies-literatureMarhelava KEuropean Research CouncilMinistry of Science and Higher Education | Narodowe Centrum Badań i Rozwoju (National Centre for Research and Development)Narodowe Centrum Nauki (National Science Centre)1395-1411https://www.ebi.ac.uk/biostudies/studies/S-EPMC12133591biostudies-literatureUnknown39(6)CD19 CAR-T cells have established a new standard for relapsed/refractory B-cell malignancies. However, the treatment fails in 50% of patients, often due to CD19 antigen loss. Alternative immunotherapies targeting other antigens are being tested but show limited efficacy, especially in cases of lineage switching or loss of B-cell phenotype, highlighting the need for novel targets. Herein, we identified leukocyte-immunoglobulin-like-receptor-B1 (LILRB1, CD85j) as a novel target for CAR-T cells through cell surface proteomics on patient-derived samples of high-risk B-cell acute lymphoblastic leukemia (B-ALL). LILRB1, an immune inhibitory receptor, is normally expressed only on monocytes and B-cells. We observed stable LILRB1 expression in B-ALL and B-cell non-Hodgkin lymphoma (B-NHL), even afLeukemiaLILRB1-directed CAR-T cells for the treatment of hematological malignancies.PMC12133591805038/STIMUNO/ERC-2018-STG805038NOR/POLNOR/ALTERCAR/0056/20192020/39/O/NZ6/014342023/49/B/NZ7/03915Lech-Maranda ELeray TMarhelava KKrawczyk MWalchli SBaranowska ISwiderska BPepek MSedek LSlota LPerkowski BForcados CInderberg EMFernandez-Fuentes NKrzywdzinska AMalinowska AVillatoro ACzerwik NMenendez PFirczuk MFidyt KWiniarska MfalseLILRB1-directed CAR-T cells for the treatment of hematological malignancies.CD19 CAR-T cells have established a new standard for relapsed/refractory B-cell malignancies. However, the treatment fails in 50% of patients, often due to CD19 antigen loss. Alternative immunotherapies targeting other antigens are being tested but show limited efficacy, especially in cases of lineage switching or loss of B-cell phenotype, highlighting the need for novel targets. Herein, we identified leukocyte-immunoglobulin-like-receptor-B1 (LILRB1, CD85j) as a novel target for CAR-T cells through cell surface proteomics on patient-derived samples of high-risk B-cell acute lymphoblastic leukemia (B-ALL). LILRB1, an immune inhibitory receptor, is normally expressed only on monocytes and B-cells. We observed stable LILRB1 expression in B-ALL and B-cell non-Hodgkin lymphoma (B-NHL), even af2025-01-01T00:00:00Z2025 Jun2026-06-03T07:53:24.767Z2026-04-26T03:10:31.399ZS-EPMC121335914018606610.1038/s41375-025-02580-z