Arginine-linked HPV-associated E7 displaying bacteria-derived outer membrane vesicles as a potent antigen-specific cancer vaccine

Suyang Wang; Chao-Cheng Chen; Ming-Hung Hu; Michelle Cheng; Hsin-Fang Tu; Ya-Chea Tsai; Jr-Ming Yang; T C Wu; Chuan-Hsiang Huang; Chien-Fu Hung

doi:10.1186/s12967-024-05195-7

Arginine-linked HPV-associated E7 displaying bacteria-derived outer membrane vesicles as a potent antigen-specific cancer vaccine

J Transl Med. 2024 Apr 22;22(1):378. doi: 10.1186/s12967-024-05195-7.

Authors

Suyang Wang¹, Chao-Cheng Chen¹, Ming-Hung Hu¹, Michelle Cheng¹, Hsin-Fang Tu¹, Ya-Chea Tsai¹, Jr-Ming Yang¹, T C Wu^{1

2

3

4}, Chuan-Hsiang Huang¹, Chien-Fu Hung^{5

6}

Affiliations

¹ Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD, 21287, USA.
² Department of Oncology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD, 21287, USA.
³ Department of Obstetrics and Gynecology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁴ Molecular Microbiology and Immunology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Pathology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD, 21287, USA. chung2@jhmi.edu.
⁶ Department of Oncology, Johns Hopkins University School of Medicine, 1550 Orleans Street, CRB II 307, Baltimore, MD, 21287, USA. chung2@jhmi.edu.

Abstract

Background: Bacteria-based cancer therapy have demonstrated innovative strategies to combat tumors. Recent studies have focused on gram-negative bacterial outer membrane vesicles (OMVs) as a novel cancer immunotherapy strategy due to its intrinsic properties as a versatile carrier.

Method: Here, we developed an Human Papillomavirus (HPV)-associated E7 antigen displaying Salmonella-derived OMV vaccine, utilizing a Poly(L-arginine) cell penetrating peptide (CPP) to enhance HPV16 E7 (aa49-67) H-2 Db and OMV affinity, termed SOMV-9RE7.

Results: Due to OMV's intrinsic immunogenic properties, SOMV-9RE7 effectively activates adaptive immunity through antigen-presenting cell uptake and antigen cross-presentation. Vaccination of engineered OMVs shows immediate tumor suppression and recruitment of infiltrating tumor-reactive immune cells.

Conclusion: The simplicity of the arginine coating strategy boasts the versatility of immuno-stimulating OMVs that can be broadly implemented to personalized bacterial immunotherapeutic applications.

Keywords: Antigen display; Bacteria outer membrane vesicle; Cancer vaccine; Tumor antigen-specific T cell; Tumor infiltrating lymphocytes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Arginine*
Bacterial Outer Membrane / immunology
Cancer Vaccines* / immunology
Female
Humans
Mice, Inbred C57BL
Papillomavirus E7 Proteins* / immunology

Substances

Arginine
Papillomavirus E7 Proteins
Cancer Vaccines
oncogene protein E7, Human papillomavirus type 16

Abstract

Publication types

MeSH terms

Substances

Grants and funding