Uncoupling tumor immunogenicity from cell death with platinum(IV)-antibody conjugates
Liu-Yi Liu1, Wenhao Yu1, Yilong Liu1
1State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
National Science Review
|June 8, 2026
Summary
New platinum-based antibody-drug conjugates (Pt-ADCs) confine platinum
Area of Science:
- Oncology
- Immunology
- Drug Development
Background:
- Platinum drugs are vital for solid tumors but cause toxicity.
- Combining platinum drugs with immunotherapy is challenging due to dosing issues.
Purpose of the Study:
- To engineer platinum(IV)-antibody conjugates (Pt-ADCs) for targeted delivery.
- To reduce systemic toxicity and enhance anti-tumor immunity.
Main Methods:
- Site-specific glycoengineering to attach Pt(IV) prodrugs.
- Mechanistic profiling of payload activation and stability.
- Evaluation in syngeneic models with PD-1 blockade.
Main Results:
- Cisplatin-derived Pt-ADCs showed efficient tumor activation.
- Cinnamate-capped variants improved stability and immune signaling.
- Pt-ADCs upregulated MHC class I and expanded T-cell responses.
- Synergy with PD-1 blockade suppressed tumor growth with low toxicity.
Conclusions:
- Pt-ADCs offer a detoxified, immunogenic approach to chemo-immunotherapy.
- This modality uncouples immune priming from high-dose cytotoxicity.
- Pt-ADCs provide a path for rational dosing in combination therapies.
Keywords:
chemo-immunotherapy combinationsplatinum(IV)–antibody conjugatestumor immunogenicityupregulation of MHC-IMore Related Videos
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