Peking University, Jan 13, 2026: A research team led by Professor Chen Peng from the College of Chemistry and Molecular Engineering at Peking University has developed a novel cancer immunotherapy strategy that forces tumors to expose themselves to the immune system. The team reports the creation of a degradation-based cancer vaccine, termed iVAC (Intratumoural Vaccination Chimera), which penetrates tumor cells, dismantles their immune defenses, and converts them into active antigen-presenting units. Published in Nature, the study offers a new solution to the long-standing challenge of immune resistance in so-called “immune-cold” tumors.
Background
Cancer immunotherapy has become a major pillar of modern cancer treatment, yet its effectiveness remains limited in many solid tumors. A central obstacle is immune evasion: tumor cells suppress immune responses by expressing checkpoint proteins such as PD-L1 while failing to present sufficient antigenic signals for T-cell recognition. As a result, many tumors remain effectively invisible to the immune system, leading to poor responses to immune checkpoint blockade therapies. Building on their earlier work in membrane protein–targeted degradation (GlueTAC/meTPD), the Chen Peng team sought to overcome immune resistance by directly reprogramming tumor cells rather than relying solely on immune-cell activation.
Why it matters
This work introduces a conceptual shift in cancer immunotherapy by transforming tumor cells from immune evaders into active participants in immune activation. Rather than merely blocking inhibitory checkpoint signals, iVAC couples immune checkpoint degradation with forced antigen presentation inside tumor cells themselves. By converting immune-cold tumors into immune-visible targets directly at the tumor site, this approach addresses a major limitation of current immunotherapies and provides a potential strategy for patients who do not respond to existing treatments.
Key Findings
The iVAC molecule acts as a molecular “Trojan horse,” entering tumor cells through a covalent nanobody-based targeting module and engaging intracellular lysosomal degradation pathways. Once internalized, iVAC induces the degradation of PD-L1, releasing immune inhibition, while simultaneously delivering engineered antigenic peptides that are processed and presented on major histocompatibility complex (MHC) molecules at the tumor cell surface. Precise molecular design, including appropriate flanking amino acid sequences around antigenic peptides, proved essential for stable and effective antigen presentation. Across tumor cell lines, mouse models, and patient-derived organoids, iVAC triggered robust T-cell activation and produced more durable antitumor responses than conventional immune checkpoint blockade therapies.
Future Implications
By coupling targeted protein degradation with intratumoural vaccination, this study expands the therapeutic potential of chemical biology in cancer treatment. The modular architecture of iVAC enables rapid adaptation to different tumor antigens, supporting the development of personalized cancer vaccines. As the research team advances toward clinical translation, this strategy may offer a powerful new avenue for treating solid tumors that remain resistant to current immunotherapies.
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Read more: https://doi.org/10.1038/s41586-025-09903-1
Written by: Akaash Babar
Edited by: Chen Shizhuo
Source: PKU WeChat (Chinese)
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