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.
Panasci et al. (Mon,) studied this question.
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