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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Active immunization combined with cisplatin confers enhanced therapeutic protection and prevents relapses of HPV-induced tumors at different anatomical sites

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Milazzotto Maldonado Porchia, Bruna Felicio [1, 2, 3] ; de Melo Moraes Aps, Luana Raposo [1, 2] ; Ramos Moreno, Ana Carolina [1] ; da Silva, Jamile Ramos [1] ; Silva, Mariangela de Oliveira [1] ; Sales, Natiely Silva [1] ; dos Santos Alves, Rubens Prince [1] ; Reily Rocha, Clarissa Ribeiro [4] ; Silva, Matheus Molina [4] ; Rodrigues, Karine Bitencourt [1] ; Barros, Tacita Borges [1] ; Pagni, Roberta Liberato [1] ; Souza, Patricia da Cruz [1] ; Diniz, Mariana de Oliveira [5, 1, 2] ; de Souza Ferreira, Luis Carlos [1]
Total Authors: 15
Affiliation:
[1] Univ Sao Paulo, Biomed Sci Inst, Dept Microbiol, Vaccine Dev Lab, Sao Paulo, SP - Brazil
[2] ImunoTera Solucoes Terapeut Ltda, Sao Paulo - Brazil
[3] Univ Sao Paulo, Biomed Sci Inst, Dept Immunol, Lab Tumor Immunol, Sao Paulo, SP - Brazil
[4] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, DNA Repair Lab, Sao Paulo - Brazil
[5] UCL, Div Infect & Immun, 5 Univ St, London WC1E 6JF - England
Total Affiliations: 5
Document type: Journal article
Source: International Journal of Biological Sciences; v. 18, n. 1, p. 15-29, 2022.
Web of Science Citations: 0
Abstract

The active immunotherapy concept relies on the use of vaccines that are capable of inducing antitumor immunity, reversion of the suppressive immunological environment, and long-term memory responses. Previously, antitumor vaccines based on a recombinant plasmid (pgDE7h) or a purified protein (gDE7) led to regression of early-established human papillomavirus (HPV)-associated tumors in a preclinical model. In this work, the anticancer vaccines were combined with cisplatin to treat HPV-induced tumors at advanced growth stages. The antitumor effects were evaluated in terms of tumor regression, induction of specific CD8+ T cells, and immune modulation of the tumor microenvironment. Acute toxicity induced by the treatment was measured by weight loss and histological alterations in the liver and kidneys. Our results revealed that the combination of cisplatin with either one of the tested immunotherapies (pgDE7h or gDE7) led to complete tumor regression in mice. Also, the combined treatment resulted in synergistic effects, particularly among mice immunized with gDE7, including activation of systemic and tumor-infiltrating E7-specific CD8+ T cells, tumor infiltration of macrophages and dendritic cells, and prevention of tumor relapses at different anatomical sites. Furthermore, the protocol allowed the reduction of cisplatin dosage and its intrinsic toxic effects, without reducing antitumor outcomes. These results expand our knowledge of active immunotherapy protocols and open perspectives for alternative treatments of HPV-associated tumors. (AU)

FAPESP's process: 11/13805-1 - Adjuvant effect of Bacillus subtilis spores co-administered with DNA vaccines
Grantee:Luana Raposo de Melo Moraes Aps
Support Opportunities: Scholarships in Brazil - Master
FAPESP's process: 20/13640-1 - Development of a T-cell-inducing vaccine against SARS-CoV-2 infection
Grantee:Luana Raposo de Melo Moraes Aps
Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
FAPESP's process: 11/20917-0 - Immunotherapy involving the E7 oncoprotein and glycoprotein D (gD) of herpes virus in vaccine formulations designed to control papillomavirus-associated tumors
Grantee:Bruna Felício Milazzotto Maldonado Porchia Ribeiro
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 17/21358-1 - Human papillomavirus (HPV)-associated neoplasia: a new therapeutic approach based on active immunotherapy through targeted stimulation of dendritic cells
Grantee:Bruna Felício Milazzotto Maldonado Porchia Ribeiro
Support Opportunities: Scholarships in Brazil - Post-Doctoral
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: 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: 18/08502-9 - Translational development and preclinical validation of an immunotherapy against tumors induced by human papillomavirus (HPV)
Grantee:Luana Raposo de Melo Moraes Aps
Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE