Restoring Tumor Cell Immunogenicity Through Ion-Assisted p53 mRNA Domestication for Enhanced In Situ Cancer...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Immunotherapy

Background:

• Tumor cell immunogenicity is a major limitation for in situ cancer vaccines (ISCVs).
• Restoring P53 function in tumor cells can enhance their immunogenicity and response to therapy.

Purpose of the Study:

• To design and evaluate PRIZE, a P53-repair nanosystem, for enhancing tumor immunogenicity and efficacy of ISCVs.
• To investigate PRIZE's ability to restore P53 levels, upregulate immune markers, and induce anti-tumor immunity.

Main Methods:

• PRIZE nanosystem developed to deliver p53 mRNA and Zn(II) to tumor cells, mimicking virus structure.
• PRIZE stabilizes p53 mRNA and extends P53 half-life, repairing P53 abnormalities in cancer cells.
• Co-delivery of indocyanine green (ICG) for photothermal therapy to induce immunogenic cell death and antigen release.

Main Results:

• PRIZE successfully repaired P53 abnormalities in P53-deficient (4T1) and P53-mutant (MC38) cells.
• Upregulation of MHC class I and CD80 on tumor cells, enhancing antigen presentation and transforming them into in situ antigen reservoirs.
• Induced ISCVs initiated the cancer immune cycle (CIC) in P53-abnormal tumor models, showing significant tumoricidal immunity and preventing metastasis and recurrence.

Conclusions:

• PRIZE nanosystem effectively enhances tumor immunogenicity by restoring P53 levels.
• PRIZE-induced ISCVs activate the cancer immune cycle, demonstrating potent anti-tumor effects.
• This approach offers a promising strategy for personalized cancer immunotherapy, combating metastasis and recurrence.