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CAR-T Cell Therapy Research / Protein Degradation and Inhibitors / Cancer Research and Treatments · Journal article
Frontiers in Immunology · September 8, 2026
A consensus or society position rather than new primary data.
This is a narrative review of targeted protein degradation (TPD) as an emerging strategy in cancer immunotherapy. The authors examine how bifunctional degraders can overcome immune evasion and therapy resistance by eliminating immunosuppressive proteins, and they outline synergies with checkpoint blockade and adoptive cell therapy, whilst identifying key translational challenges in delivery, toxicity, and clinical optimization.
Journal article. Cancer patients undergoing immunotherapy; focus on overcoming immune evasion and therapy resistance..
TPD harnesses ubiquitin–proteasome system and lysosomal pathways to eliminate disease-causing proteins refractory to conventional inhibition. TPD can reprogram the tumor microenvironment from 'cold' to 'hot' immunological states by dismantling immunosuppressive nodes. TPD demonstrates synergy with immune checkpoint blockade and adoptive cell therapy.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
This review provides a framework for understanding how targeted protein degradation may address limitations of conventional inhibitors and checkpoint blockade in cancer immunotherapy. Clinicians and researchers should consider TPD as a potential strategy to overcome immune evasion, though the review emphasizes that translational roadblocks in delivery, therapeutic window, and toxicity mitigation remain to be solved before widespread clinical implementation.
A comprehensive review summarizing molecular principles, clinical progress, and translational strategies for targeted protein degradation in cancer immunotherapy, rather than reporting original experimental data or trial results.
This review provides a framework for understanding how targeted protein degradation may address limitations of conventional inhibitors and checkpoint blockade in cancer immunotherapy. Clinicians and researchers should consider TPD as a potential strategy to overcome immune evasion, though the review emphasizes that translational roadblocks in delivery, therapeutic window, and toxicity mitigation remain to be solved before widespread clinical implementation.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
What is missing. This record has no reported figures. That is a gap in the analysis, not a judgement about the study.
Targeted protein degradation (TPD) harnesses endogenous proteolytic machineries—the ubiquitin–proteasome system and lysosomal pathways—to selectively eliminate disease-causing proteins that are refractory to conventional inhibition. In cancer immunotherapy, TPD dismantles critical immunosuppressive nodes across extracellular, membrane and intracellular compartments, reprogramming the tumor microenvironment from an immunologically ‘cold’ to a ‘hot’ state. This Review examines the molecular engineering principles of bifunctional degraders and summarizes clinical progress demonstrating synergy with immune checkpoint blockade and adoptive cell therapy. We discuss how catalytic protein elimination overcomes primary immune evasion and adaptive resistance driven by compensatory signaling, target mutation and metabolic rewiring. Finally, we outline translational roadblocks in cell-specific delivery, therapeutic window optimization and on-target/off-tissue toxicity mitigation, and propose engineering strategies to advance the clinical implementation of targeted protein degradation in immuno-oncology.
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