The role of the CD200/CD200 receptor axis on CAR T cells against paediatric acute lymphoblastic B-lineage leukaemia

Mate, Wyona Claire (2025): The role of the CD200/CD200 receptor axis on CAR T cells against paediatric acute lymphoblastic B-lineage leukaemia. Dissertation, LMU München: Medizinische Fakultät

Abstract

Acute lymphoblastic leukaemia represents the most frequent malignancy in childhood. Despite impressive progress in the treatment of this disease, the long-term outcome for children suffering from primary therapy failure or relapse is still unsatisfying. Over the past few years, chimeric antigen receptor (CAR) T cells have proven to be as an auspicious approach in the fight of primary refractory or relapsed paediatric leukaemia. But even though CAR T cells archived high initial responds rates, most patients missed long-term remissions, making CAR T cells perfectible. It is known that cancer cells have the potential to create an immunosuppressive micromilieu by interacting with their environment. The immunoregulatory CD200/CD200 receptor (CD200R) axis is considered to play a crucial role in this interaction. As CD200 is abundantly expressed on leukaemic blasts, we aimed to investigate the implications of CD200 expressing acute B cell lymphoblastic leukaemia on immune cells. Therefore, we performed co-culture experiments of leukaemic cells lines and different immune cells including T cells, CAR T cells, macrophages and dendritic cells. We found that CD200 on B cell leukaemic blasts directly inhibit T cell and CAR T cell functionality in vitro depending on CD200R density and level of activation. Additionally, we developed two potent attempts of overcoming CD200 induced CAR T cell impairment: CD200R knock-out CAR T cells and CD200R-CD28 fusion receptor CAR T cells. All in all, we gained better understanding of the CD200-mediated interaction between leukaemic blasts and immune cells allowing us to enhance CAR T cell therapy for primary refractory or relapsed acute lymphoblastic leukaemia.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: ALL, Leukämie, T cells, CD200, CD200R
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 27. November 2025
• 1. Bericht­erstatter:in: Feuchtinger, Tobias