Salmonella immunotherapy engineered with highly efficient tumor antigen coating establishes antigen-specific CD8+ T cell immunity and increases in antitumor efficacy with type I interferon combination therapy

ABSTRACT

Bacteria-based cancer therapy employs various strategies to combat tumors, one of which is delivering tumor-associated antigen (TAA) to generate specific immunity. Here, we utilized a poly-arginine extended HPV E7 antigen (9RE7) for attachment on Salmonella SL7207 outer membrane to synthesize the bacterial vaccine Salmonella-9RE7 (Sal-9RE7), which yielded a significant improvement in the amount of antigen presentation compared to the previous lysine-extended antigen coating strategy. In TC-1 tumor mouse models, Sal-9RE7 monotherapy decreased tumor growth by inducing E7 antigen-specific immunity. In addition, pairing Sal-9RE7 with adjuvant Albumin-IFNβ (Alb-IFNβ), a protein cytokine fusion, the combination significantly increased the antitumor efficacy and enhanced immunogenicity in the tumor microenvironment (TME). Our study made a significant contribution to personalized bacterial immunotherapy via TAA delivery and demonstrated the advantage of combination therapy.

KEYWORDS:

• Bacterial immunotherapy
• CD8+ T cell
• Cell penetrating peptide
• Cervical cancer
• Salmonella
• Tumor antigen
• Type I inteferon

Acknowledgments

We thank the laboratory animal center at the Johns Hopkins School of Medicine for animal care.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and material

All data relevant to the study are included in the article or uploaded as supplementary information. Data and materials are available on reasonable request.

Authors’ contributions

Conception and design: S.W., CF.H.

Conducting experiments: S.W., CC.C., YC.T.

Analysis and interpretation of data: S.W., CY.C., YC.T. JM.Y.

Writing and review of manuscript: S.W., M.C., CF.H.

Study supervision: T.C. W, CH.H., CF.H.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/2162402X.2023.2298444.

Additional information

Funding

This study was supported by the National Institutes of Health, National Cancer Institute Specialized Program of Research Excellence (SPORE) in Cervical Cancer grant (NIH/NCI P50CA098252) and NCI awards (R01CA237067, R21DE029910-01, R21CA256020, and 1R21CA234516-01A1).