Description

• Tytuł:
  LILRB1-directed CAR-T cells for the treatment of hematological malignancies
• Twórca:
  Marhelava, Katsiaryna;
  Fidyt, Klaudyna;
  Pepek, Monika;
  Krawczyk, Marta;
  Forcados, Christopher;
  Malinowska, Agata;
  Świderska, Bianka;
  Fernandez-Fuentes, Narcis;
  Czerwik, Natalia;
  Baranowska, Iwona;
  Krzywdzinska, Agnieszka;
  Sedek, Lukasz;
  Slota, Lukasz;
  Perkowski, Bartosz;
  Villatoro, Alicia;
  Leray, Thibault;
  Lech-Maranda, Ewa;
  Menendez, Pablo;
  Inderberg, Else Marit;
  Wälchli, Sébastien;
  Winiarska, Magdalena;
  Firczuk, Malgorzata
• Opis:
  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 after CD20/CD19-based immunotherapies. LILRB1 CAR-T cells showed antigen-specific antitumor activity in vitro against B-ALL/B-NHL cells, including those resistant to CD19 CAR-T-cells, and in vivo in B-ALL xenografts. Additionally, we identified LILRB1 in monocytic acute myeloid leukemia (AML) and demonstrated LILRB1 CAR-T cell cytotoxicity against AML cell lines in vitro and in vivo. These findings establish LILRB1 as a novel target for cancer immunotherapy and show evidence for the preclinical efficacy of LILRB1 CAR-T cells against haematological malignancies, including cases resistant to previous lines of immunotherapy, thus holding promise for further clinical development.
• Dostępność obiektu:
  free access
• Data:
  2025
• Typ:
  Article;
  PeerReviewed
• Język:
  English
• Format:
  application/pdf
• Relacja: http://eprints.ibb.waw.pl/2543 ;http://doi.org/10.1038/s41375-025-02580-z ;doi:10.1038/s41375-025-02580-z
• Temat i słowa kluczowe:
  R Medicine (General);
  RM Therapeutics. Pharmacology
• Identyfikator: http://eprints.ibb.waw.pl/2543/1/s41375-025-02580-z.pdf ;
  Marhelava, Katsiaryna and Fidyt, Klaudyna and Pepek, Monika and Krawczyk, Marta and Forcados, Christopher and Malinowska, Agata and Świderska, Bianka and Fernandez-Fuentes, Narcis and Czerwik, Natalia and Baranowska, Iwona and Krzywdzinska, Agnieszka and Sedek, Lukasz and Slota, Lukasz and Perkowski, Bartosz and Villatoro, Alicia and Leray, Thibault and Lech-Maranda, Ewa and Menendez, Pablo and Inderberg, Else Marit and Wälchli, Sébastien and Winiarska, Magdalena and Firczuk, Malgorzata (2025) LILRB1-directed CAR-T cells for the treatment of hematological malignancies. Leukemia . ISSN 0887-6924
• Dostawca danych:
  Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk
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