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CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.

作者信息

Abken Hinrich

机构信息

Leibniz Institute for Immunotherapy, Genetic Immunotherapy Division, Regensburg, Germany.

Genetic Immunotherapy, University of Regensburg, Regensburg, Germany.

出版信息

Nat Rev Gastroenterol Hepatol. 2025 Apr 14. doi: 10.1038/s41575-025-01062-y.


DOI:10.1038/s41575-025-01062-y
PMID:40229574
Abstract

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.

摘要

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CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.

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[1]
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[2]
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[3]
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[CAR T cells in solid tumors: resistance mechanisms].

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本文引用的文献

[1]
: a new therapeutic target for immune evasion of colorectal cancer.

J Clin Pathol. 2025-5-11

[2]
LGR5 as a diagnostic marker for dysplasia in serrated polyps.

J Clin Pathol. 2025-1-9

[3]
Spatially organized tumor-stroma boundary determines the efficacy of immunotherapy in colorectal cancer patients.

Nat Commun. 2024-11-26

[4]
Novel Therapies for Pancreatic Cancer.

JCO Oncol Pract. 2025-5

[5]
Enhanced tumor control and survival in preclinical models with adoptive cell therapy preceded by low-dose radiotherapy.

Front Oncol. 2024-10-9

[6]
Automated manufacturing and characterization of clinical grade autologous CD20 CAR T cells for the treatment of patients with stage III/IV melanoma.

Front Immunol. 2024

[7]
Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancers.

Clin Cancer Res. 2024-12-2

[8]
Chimeric Antigen Receptor T Cells Targeting CD19 and GCC in Metastatic Colorectal Cancer: A Nonrandomized Clinical Trial.

JAMA Oncol. 2024-11-1

[9]
STRIvE-02: A First-in-Human Phase I Study of Systemically Administered B7-H3 Chimeric Antigen Receptor T Cells for Patients With Relapsed/Refractory Solid Tumors.

J Clin Oncol. 2024-12-10

[10]
Activation of Cell-Intrinsic Signaling in CAR-T Cells via a Chimeric IL7R Domain.

Cancer Res Commun. 2024-9-1

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