Advances in cancer immunotherapy: adoptive cell therapy and immune cell engagers in solid tumours

Adoptive cell therapies (ACT) and immune cell engagers (ICE) redirect or potentiate immune effector function against immune-tolerated antigens expressed on malignant cells, representing a distinct class of engineered immunotherapies beyond immune checkpoint blockade. These strategies have been particularly successful in hematologic malignancies; however, translation to solid tumours has been constrained by antigen heterogeneity, limited immune cell trafficking and persistence, an immunosuppressive tumour microenvironment, and on-target off-tumour toxicity. Despite these barriers, accumulating data and clinical experience with these therapies in solid tumours demonstrate feasibility, scalability, safety, and meaningful clinical activity. In light of recent regulatory approvals of ACT and ICE in solid tumours, we aim to provide a comprehensive clinician-oriented overview of these evolving therapeutic platforms. Herein, we review principles of antigen selection, mechanisms underlying investigational ACT and ICE, current barriers to clinical translation in solid tumours, strategies to overcome these limitations, and future prospects for immune-redirecting drug development in solid tumours.

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Publication Details

Journal
British Journal of Cancer
Published
2026-04-27
DOI
https://doi.org/10.1038/s41416-026-03450-w
Primary Topic
CAR-T cell therapy research
Type
article
Field-Weighted Citation Impact
0.00
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article

Advances in cancer immunotherapy: adoptive cell therapy and immune cell engagers in solid tumours

Lillian L. Siu, Ben Tran, Justin Panasci, Changsu Lawrence Park
British Journal of Cancer
CAR-T cell therapy research
article

Advances in cancer immunotherapy: adoptive cell therapy and immune cell engagers in solid tumours

Lillian L. Siu, Ben Tran, Justin Panasci, Changsu Lawrence Park
article en

Abstract

Adoptive cell therapies (ACT) and immune cell engagers (ICE) redirect or potentiate immune effector function against immune-tolerated antigens expressed on malignant cells, representing a distinct class of engineered immunotherapies beyond immune checkpoint blockade. These strategies have been particularly successful in hematologic malignancies; however, translation to solid tumours has been constrained by antigen heterogeneity, limited immune cell trafficking and persistence, an immunosuppressive tumour microenvironment, and on-target off-tumour toxicity. Despite these barriers, accumulating data and clinical experience with these therapies in solid tumours demonstrate feasibility, scalability, safety, and meaningful clinical activity. In light of recent regulatory approvals of ACT and ICE in solid tumours, we aim to provide a comprehensive clinician-oriented overview of these evolving therapeutic platforms. Herein, we review principles of antigen selection, mechanisms underlying investigational ACT and ICE, current barriers to clinical translation in solid tumours, strategies to overcome these limitations, and future prospects for immune-redirecting drug development in solid tumours.

British Journal of Cancer
University Health Network (CA), Peter MacCallum Cancer Centre (AU), Princess Margaret Cancer Centre (CA)
Good health and well-being
Openalex Percentile: Top 7%
CAR-T cell therapy research
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