Full Text | PDF

Int J Biol Sci 2022; 18(1):15-29. doi:10.7150/ijbs.56644 This issue Cite

Research Paper

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

Bruna Felício Milazzotto Maldonado Porchia^1,2,*, Luana Raposo de Melo Moraes Aps^1,2, Ana Carolina Ramos Moreno¹, Jamile Ramos da Silva¹, Mariângela de Oliveira Silva¹, Natiely Silva Sales¹, Rubens Prince dos Santos Alves¹, Clarissa Ribeiro Reily Rocha³, Matheus Molina Silva³, Karine Bitencourt Rodrigues¹, Tácita Borges Barros¹, Roberta Liberato Pagni¹, Patrícia da Cruz Souza¹, Mariana de Oliveira Diniz^1,2,#, Luís Carlos de Souza Ferreira^1✉

1. Vaccine Development Laboratory, Department of Microbiology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, SP, Brazil
2. ImunoTera Soluções Terapêuticas Ltda
3. DNA Repair Laboratory, Department of Microbiology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil
Porchia, BFMM and Aps, LRMM contributed equally to this work.
* Present address: Laboratory of Tumor Immunology, Department of Immunology, Biomedical Sciences Institute, University of Sao Paulo, Sao Paulo, SP, Brazil
# Present address: Division of Infection and Immunity, University College London, 5 University St, Bloomsbury WC1E 6JF, London

✉ Corresponding author: Luís C. S. Ferreira. Av. Prof. Lineu Prestes, 1374, Sao Paulo - SP, Brazil, Zip code: 05508-000. Phone: +55 11 30917356. E-mail address: lcsfbr

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.

Keywords: Cancer, HPV, vaccine, gDE7, immunotherapy

Citation styles

©2024 Ivyspring International Publisher. Terms of use