Antigen Delivery to DEC205(+) Dendritic Cells Induces Immunological Memory and Protective Therapeutic Effects against HPV-Associated Tumors at Different Anatomical Sites

Author(s):Show less -

Silva, Mariangela O. ^[1] ; Almeida, Bianca S. ^[2] ; Sales, Natiely S. ^[1] ; Diniz, Mariana O. ^{[3, 1]} ; Aps, Luana R. M. M. ^[1] ; Rodrigues, Karine B. ^[1] ; Silva, Jamile R. ^[1] ; Moreno, Ana C. R. ^[1] ; Porchia, Bruna F. M. M. ^[1] ; Sulczewski, Fernando B. ^[2] ; Boscardin, Silvia B. ^[2] ; Ferreira, Luis C. S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Vaccine Dev Lab, Dept Microbiol, Inst Biomed Sci, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Lab Antigen Targeting Dendrit Cells, Dept Parasitol, Inst Biomed Sci, Sao Paulo - Brazil

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

• Document type: Journal article
• Source: International Journal of Biological Sciences; v. 17, n. 11, p. 2944-2956, 2021.
• Web of Science Citations: 0

Abstract

The generation of successful anticancer vaccines relies on the ability to induce efficient and long-lasting immune responses to tumor antigens. In this scenario, dendritic cells (DCs) are essential cellular components in the generation of antitumor immune responses. Thus, delivery of tumor antigens to specific DC populations represents a promising approach to enhance the efficiency of antitumor immunotherapies. In the present study, we employed antibody-antigen conjugates targeting a specific DC C-type lectin receptor. For that purpose, we genetically fused the anti-DEC205 monoclonal antibody to the type 16 human papillomavirus (HPV-16) E7 oncoprotein to create a therapeutic vaccine to treat HPV-associated tumors in syngeneic mouse tumor models. The therapeutic efficacy of the alpha DEC205-E7 mAb was investigated in three distinct anatomical tumor models (subcutaneous, lingual and intravaginal). The immunization regimen comprised two doses of the alpha DEC205-E7 mAb coadministered with a DC maturation stimulus (Polyinosinic:polycytidylic acid, poly (I:C)) as an adjuvant. The combined immunotherapy produced robust antitumor effects on both the subcutaneous and orthotopic tumor models, stimulating rapid tumor regression and long-term survival. These outcomes were related to the activation of tumor antigen-specific CD8(+) T cells in both systemic compartments and lymphoid tissues. The alpha DEC205-E7 antibody plus poly (I:C) administration induced long-lasting immunity and controlled tumor relapses. Our results highlight that the delivery of HPV tumor antigens to DCs, particularly via the DEC205 surface receptor, is a promising therapeutic approach, providing new opportunities for the development of alternative immunotherapies for patients with HPV-associated tumors at different anatomical sites. (AU)

• FAPESP's process: 18/26515-0 - Antigen targeting to dendritic cells as a strategy to improve the efficiency of immunotherapies to HPV-16-associated tumors.
• Grantee: Luis Carlos de Souza Ferreira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/07629-5 - Targeting antigens to dendritic cells as an immunotherapeutic strategy to control HPV-induced tumors
• Grantee: Mariângela de Oliveira Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• 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: 16/00708-1 - 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: 18/07142-9 - Influence of STAT1, STAT3, STAT5 and STAT6 Signaling Pathways on Conventional Dendritic Cells in the Instruction of the T-Cell Auxiliary Response
• Grantee: Silvia Beatriz Boscardin
• Support Opportunities: Regular Research Grants