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Challenges and successes in cellular therapies and CAR-T: insights from the 50th EBMT annual meeting

Bone Marrow Transplantation (2024)Cite this article

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Chimeric-antigen receptor T-cell (CAR-T) therapy is a novel cellular therapy whereby T-cells are collected via apheresis and genetically modified to target specific antigens, e.g. CD19 on B cells, then reinfused after lymphodepleting chemotherapy [1]. The first adult patient received CAR-T therapy in 2010 for refractory chronic lymphocytic leukaemia and the first paediatric patient received CAR-T therapy in 2012 for refractory B-cell acute lymphoblastic leukaemia (ALL) [1]. In the 14 years since, CAR-T therapy has grown substantially with research aiming to expand its usage into other indications. However, generating CAR-T to target antigens other than those on B-cells poses various challenges. Exciting new results in the development of novel cellular therapies and CAR-T for both paediatric and adult patients were presented at the 50th annual European Society for Blood and Marrow Transplantation (EBMT) Congress in Glasgow, Scotland in April 2024.

Naldini et al. [8] described the efficient engineering of a population of tumour-associated Tie-2 expressing monocytes/macrophages (TEMs) naturally infiltrating the tumour micro-environment (TME) to precisely deliver Interferon-α (IFN-α). By transplanting hematopoietic stem and progenitor cells (HSPC) transduced with a lentiviral vector expressing IFN-α, under the positive regulation of the Tie-2 enhancer/promoter, a specific release of IFN-α in the TME was assessed, favouring immune activation and therapeutic activity in different preclinical tumour models [9,10,11]. Based on these findings, Birocchi and colleagues [12] described an inducible platform for a precise, spatial-temporal regulated cytokine delivery within the TME. This has been combined with adoptive T-cell therapies such as CAR-T and tumour targeted gene therapy in preclinical models with promising results [13], paving the way for clinical trials.

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Fig. 1: Key challenges in CAR-T therapy for T-cell ALL.
Fig. 2: Key challenges in CAR-T therapy for solid tumours.
Fig. 3: Targeted cancer gene therapy for glioblastoma multiforme.
Fig. 4: Anti-CD19 CAR-T targets in autoimmune diseases.

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Acknowledgements

This paper has been produced on behalf of the EBMT Trainee Committee, and the Cellular Therapy and Immunobiology working parties of the EBMT

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  1. These authors contributed equally: Katherine S. Colman, Giorgio Orofino.

Authors and Affiliations

  1. Children’s Cancer Centre, Royal Children’s Hospital, Melbourne, VIC, Australia

    Katherine S. Colman

  2. Haematology and Bone Marrow Transplant Unit, IRCCS San Raffaele Hospital, Milano, Italy

    Giorgio Orofino & Annalisa Ruggeri

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KC and GO wrote and edited the manuscript, AR provided guidance and edited the manuscript. All authors approved the final version.

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Correspondence to Katherine S. Colman or Giorgio Orofino.

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Colman, K.S., Orofino, G. & Ruggeri, A. Challenges and successes in cellular therapies and CAR-T: insights from the 50th EBMT annual meeting. Bone Marrow Transplant (2024). https://doi.org/10.1038/s41409-024-02369-1

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