Expression of a soluble IL-10 receptor enhances the therapeutic effects of a papillomavirus-associated antitumor vaccine in a murine model

Author(s)

Silva, Jamile R. ^[1] ; Sales, Natiely S. ^[1] ; Silva, Mariangela O. ^[1] ; Aps, Luana R. M. M. ^[1] ; Moreno, Ana C. R. ^[1] ; Rodrigues, Elaine G. ^[2] ; Ferreira, Luis C. S. ^[1] ; Diniz, Mariana O. ^{[3, 1]}

Affiliation

^[1] Univ Sao Paulo, Biomed Sci Inst, Dept Microbiol, Vaccine Dev Lab, Av Prof Lineu Prestes 1374, BR-05508000 Sao Paulo, SP - Brazil

^[2] Univ Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Immunol & Parasitol, Tumor Immunobiol Lab, Sao Paulo - Brazil

^[3] UCL, Div Infect & Immun, 5 Univ St, London WC1E 6JF - England

• Document type: Journal article
• Source: CANCER IMMUNOLOGY IMMUNOTHERAPY; v. 68, n. 5, p. 753-763, MAY 2019.
• Web of Science Citations: 1

Abstract

The presence of IL-10, produced either by tumor cells or immunosuppressive cells, is frequently associated with a poor prognosis for cancer progression. It may also negatively impact anticancer treatments, such as immunotherapies, that otherwise would promote the activation of cytotoxic T cells capable of detecting and destroying malignant cells. In the present study, we evaluated a new adjuvant approach for anticancer immunotherapy using a plasmid vector encoding a soluble form of the IL-10 receptor (pIL-10R). pIL-10R was coadministered to mice with a DNA vaccine encoding the type 16 human papillomavirus (HPV-16) E7 oncoprotein genetically fused with glycoprotein D of herpes simplex virus (HSV) (pgDE7h). Immunization regimens based on the coadministration of pIL-10R and pgDE7h enhanced the antitumor immunity elicited in mice injected with TC-1 cells, which express HPV-16 oncoproteins. The administration of the DNA vaccines by in vivo electroporation further enhanced the anticancer effects of the vaccines, leading to the activation of tumor-infiltrating polyfunctional E7-specific cytotoxic CD8(+) T cells and control of the expansion of immunosuppressive cells. In addition, the combination of immunotherapy and pIL-10R allowed the control of tumors in more advanced growth stages that otherwise would not be treatable by the pgDE7h vaccine. In conclusion, the proposed treatment involving the expression of IL-10R enhanced the antitumor protective immunity induced by pgDE7h administration and may contribute to the development of more efficient clinical interventions against HPV-induced tumors. (AU)

• FAPESP's process: 16/00708-1 - Indoleamine 2,3 dioxygenase in the biology of papillomaviruses-induced tumors: neoadjuvant effects on the immunetherapy of tumors
• Grantee: Ana Carolina Ramos Moreno
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 16/14344-1 - Control tumors induced by HPV -based immunotherapy in combination monoclonal antibodies blocking immunosuppressive pathways a therapeutic vaccine capable of activating CD8 + cytotoxic T lymphocytes
• Grantee: Natiely Silva Sales
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/16505-0 - Indoleamine 2,3 dioxygenase in the biology of papillomaviruses-induced tumors: neoadjuvant effects on the immunetherapy of tumors
• Grantee: Ana Carolina Ramos Moreno
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/11397-7 - Targeting antigens to dendritic cells as an immunotherapeutic strategy to control HPV-induced tumors
• Grantee: Mariângela de Oliveira Silva
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 13/15360-2 - New therapeutic frontiers against tumors caused by human papilloma virus (HPV): experimental evaluation of the chemotherapy in association to vaccine strategies
• Grantee: Luana Raposo de Melo Moraes Aps
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/51218-0 - Immunotherapy against human papillomavirus (HPV) induced tumors
• Grantee: Mariana de Oliveira Diniz
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/11073-1 - Co-expression of IL-10 receptor as a strategy to enhance the effects of a DNA vaccine focused on the control of tumors induced by HPV-16
• Grantee: Jamile Ramos da Silva
• Support Opportunities: Scholarships in Brazil - Master