Combining STING-based neoantigen-targeted vaccine with checkpoint modulators enhances antitumor immunity in murine...

Area of Science:

• Oncology
• Immunology
• Vaccine Development

Background:

• Tumor neoantigens are promising targets for cancer vaccines due to their low likelihood of central immune tolerance.
• Pancreatic cancer remains a significant challenge, often associated with poor immunogenicity.

Purpose of the Study:

• To develop and evaluate a neoantigen-targeted vaccine (PancVAX) for pancreatic cancer.
• To assess the efficacy of PancVAX in combination with immune checkpoint modulators.

Main Methods:

• Whole-exome sequencing and RNA sequencing were used to identify neoantigens.
• An in silico immunogenicity prediction algorithm (NetMHC) was employed for neoantigen selection.
• PancVAX was administered with a STING adjuvant (ADU-V16) to mice with pancreatic adenocarcinoma (Panc02).
• Combination therapy included anti-PD-1 and agonist OX40 antibodies.

Main Results:

• PancVAX activated neoepitope-specific T cells and induced transient tumor regression.
• Combination therapy with PancVAX, anti-PD-1, and OX40 antibodies resulted in enhanced, durable tumor regression and survival benefit.
• The addition of OX40 reduced T cell exhaustion markers (Lag3, PD-1) and led to tumor rejection upon rechallenge, indicating T cell memory induction.

Conclusions:

• Personalized neoantigen-based vaccines combined with immune checkpoint modulators represent a viable strategy for pancreatic and other non-immunogenic cancers.
• This approach may overcome immune tolerance and induce durable anti-tumor immunity.