Abken Hinrich
Leibniz Institute for Immunotherapy, Genetic Immunotherapy Division, Regensburg, Germany.
Genetic Immunotherapy, University of Regensburg, Regensburg, Germany.
Nat Rev Gastroenterol Hepatol. 2025 Apr 14. doi: 10.1038/s41575-025-01062-y.
Despite multimodal treatment options, most gastrointestinal cancers are still associated with high mortality rates and poor responsiveness to immunotherapy. The unprecedented efficacy of chimeric antigen receptor (CAR)-engineered T cells in the treatment of haematological malignancies raised interest in translating CAR T cell therapies to the treatment of gastrointestinal cancers. Treatment of solid cancers with canonical CAR T cells faces substantial challenges, including the dense architecture of the tumour tissue, the tolerogenic environment with low tumour-intrinsic immunogenicity, the rareness of targetable tumour-selective antigens, the antigenic heterogeneity of cancer cells, and the profound metabolic and immune cell disbalances. This Review provides an overview of CAR T cell trials in the treatment of gastrointestinal cancers, discussing considerations relating to safety, efficacy, potential reasons for failure and options for improving CAR T cells for the future. In addition, lessons regarding how to improve efficacy are drawn from CAR T cells armed with adjuvants that sustain their activation within the hostile environment and activate resident immune cells. As the field is rapidly evolving, current treatment modalities and editing CAR T cell functionalities are being refined towards a potentially more successful CAR T cell therapy for gastrointestinal cancers.
Nat Rev Gastroenterol Hepatol. 2025-4-14
Cochrane Database Syst Rev. 2021-9-13
Int Rev Immunol. 2025-6-19
Mol Ther. 2024-11-26
Curr Opin HIV AIDS. 2024-7-1
Mol Cancer. 2025-7-26
Front Immunol. 2025-6-12
Inn Med (Heidelb). 2025-6-25
J Clin Pathol. 2025-5-11
J Clin Pathol. 2025-1-9
JCO Oncol Pract. 2025-5
Cancer Res Commun. 2024-9-1