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PROTACs in cancer immunotherapy: a minireview
Köckenberger J E1, Cardenas Alcoser E S2,3, Chang E T1
1Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, 92093, U.S.A.
Biochemical Society Transactions
|October 1, 2025
Summary
Proteolysis-targeting chimeras (PROTACs) offer a novel approach to cancer immunotherapy by degrading proteins that enable tumor immune escape. This strategy enhances the immune response and inhibits immune suppression for improved cancer treatment.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Immune checkpoint blockade (ICB) has advanced cancer therapy, but limited response rates necessitate new strategies.
- Tumor immune escape mechanisms remain a significant challenge in cancer treatment.
- Proteolysis-targeting chimeras (PROTACs) represent a promising preclinical development for cancer immunotherapy.
Purpose of the Study:
- To review ongoing research on employing PROTACs in cancer immunotherapy.
- To highlight the potential of PROTACs in enhancing anti-tumor immune responses.
- To discuss how PROTACs can overcome tumor immune suppression.
Main Methods:
- Review of preclinical research and scientific literature on PROTACs in cancer immunotherapy.
- Analysis of PROTACs' mechanism of action in targeting tumor immune escape signaling.
- Evaluation of PROTAC-induced protein degradation and its impact on the tumor microenvironment.
Main Results:
- PROTACs can pharmacologically induce targeted protein degradation, inhibiting non-enzymatic functions and protein-protein interactions.
- PROTAC-induced degradation alters the major histocompatibility complex I ligandome, acting as an immune stimulus.
- PROTACs show potential in modulating immune suppression and enhancing cancer immune response.
Conclusions:
- PROTACs offer a unique mechanism to interfere with tumor immune escape signaling.
- Targeted protein degradation by PROTACs can enhance cancer immunotherapy efficacy.
- Further research into PROTACs holds significant promise for developing novel cancer treatments.
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