Adenoviral vaccine targeting multiple neoantigens as strategy to eradicate large tumors combined with checkpoint...

Area of Science:

• Oncology
• Immunology
• Vaccinology

Background:

• Neoantigens (nAgs) are key targets for cancer vaccines, stimulating potent T cell responses.
• Great Ape-derived Adenovirus (GAd) vectors effectively induce T cell-mediated immunity in humans.

Purpose of the Study:

• To evaluate the efficacy of a novel GAd vector encoding multiple neoantigens for cancer treatment.
• To assess the combined effect of GAd-neoantigen vaccination and checkpoint inhibitors on tumor eradication.

Main Methods:

• Prophylactic and early therapeutic vaccination in mouse tumor models.
• Combination therapy using GAd-neoantigen vaccine and anti-PD1 checkpoint inhibitors.
• Gene expression profiling and T cell receptor (TCR) repertoire analysis of regressing tumors.

Main Results:

• GAd vaccination alone controlled tumor growth in mice.
• Combination therapy with GAd and anti-PD1 eradicated large tumors.
• Enhanced infiltration and diversification of T cells were observed in tumors treated with combination therapy.

Conclusions:

• GAd-based neoantigen vaccines are effective in controlling tumor growth.
• Eradication of large tumors requires combining GAd vaccination with checkpoint blockade.
• Vaccine efficacy correlates with the breadth of neoantigen-specific T cells and requires overcoming tumor-induced suppression.