Vaccines targeting p53 mutants elicit anti-tumor immunity

Area of Science:

• Oncology
• Immunology
• Vaccine Development

Background:

• p53 tumor suppressor mutations are frequent in cancers, lacking effective targeted therapies.
• The p53 S237G mutant is highly expressed in A20 murine tumor cells, presenting a therapeutic target.

Purpose of the Study:

• To develop and evaluate a DNA vaccine (gWIZ-S237G) targeting the p53 S237G mutant.
• To assess the vaccine's efficacy alone and in combination with PD-1 blockade against A20 tumors and liver metastasis.

Main Methods:

• Intramuscular administration of the gWIZ-S237G DNA vaccine via electroporation.
• Combination therapy with PD-1 blockade.
• Assessment of anti-tumor immune responses, including T cell infiltration, dendritic cell maturation, and antibody production.
• Evaluation in subcutaneous A20 tumor and A20 liver metastasis models.

Main Results:

• The anti-p53-S237G vaccine induced robust protective responses against A20 tumors and liver metastasis.
• Vaccination enhanced immune cell infiltration (CD8+ T cells, NK cells, DCs) and dendritic cell maturation.
• The vaccine stimulated tumor-specific antibodies and Th1/CD8+ T cell responses, including multifunctional CD8+ T cells secreting IFN-γ and TNF-α.
• Long-term anti-tumor effects were observed, dependent on memory CD8+ T cells.
• Combination with PD-1 blockade showed superior tumor growth and metastasis inhibition.

Conclusions:

• Targeting p53 mutants via vaccination is a viable precision medicine approach for p53-mutated cancers.
• The gWIZ-S237G DNA vaccine elicits potent anti-tumor immunity and has therapeutic potential.
• Combination therapy with PD-1 blockade enhances vaccine efficacy.