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

Autor(es):Mostrar menos -

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]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: International Journal of Biological Sciences; v. 17, n. 11, p. 2944-2956, 2021.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/26515-0 - Direcionamento de antígenos para células dendríticas como estratégia para melhorar a eficiência de imunoterapias contra tumores associados ao HPV-16.
• Beneficiário: Luis Carlos de Souza Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07629-5 - Direcionamento de antígenos para células dendríticas como estratégia imunoterapêutica para o controle de tumores associados ao HPV
• Beneficiário: Mariângela de Oliveira Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 15/16505-0 - Indoleamina 2,3 dioxigenase (IDO) na biologia de tumores associados aos papilomavírus humano (HPV): efeitos neoadjuvantes na imunoterapia tumoral
• Beneficiário: Ana Carolina Ramos Moreno
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 16/00708-1 - Indoleamina 2,3 dioxigenase (IDO) na biologia de tumores associados aos papilomavírus humano (HPV): efeitos neoadjuvantes na imunoterapia tumoral
• Beneficiário: Ana Carolina Ramos Moreno
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 18/07142-9 - Influência das Vias de Sinalização de STAT1, STAT3, STAT5 e STAT6 em Células Dendríticas Convencionais na Instrução da Resposta de Células T Auxiliares
• Beneficiário: Silvia Beatriz Boscardin
• Modalidade de apoio: Auxílio à Pesquisa - Regular