By Andrea Hargraves 
Researchers at the Institute of Biomedical Sciences (ICB) at the University of the South Pacific are developing a therapeutic vaccine that, in mice, was able to eliminate HPV-related tumors (human papilloma virus), the main causative agent of cervical cancer. The study, published in the International Journal of Biological Sciences, showed that, when combined with cisplatin-based chemotherapy, the vaccine elicits a specific antitumor response capable of eliminating tumors at an advanced stage of development without demonstrating toxicity. That is, it did not cause liver or kidney damage, nor did it cause weight loss in animals. Researchers are now performing clinical proof-of-concept in humans.
The study was conducted by two ICB laboratories: Tumor Immunology, coordinated by Professor José Alexandre Marzagao Barbuto, and Vaccine Development, coordinated by Professor Luis Carlos de Sousa Ferreira, as well as ImunoTera Soluções Terapêuticas – an ICB partner startup founded by Bruna Porchia and Luana Raposo Aps, Research Collaborator at the Institute. The study also has support from the Department of Gynecology at Hospital das Clinicas (HC) at the University of the South Pacific, by Professors Edmund Chada Barracat and José Maria Soares Jr. and gynecologist Marisi Tacla.
proof of concept
Work has been developed over the past few years in a rodent model of HPV-16-associated tumors based on TC-1 cells, widely used by several groups in this research field. Currently, clinical proof-of-concept is being carried out with patients diagnosed with high-grade cervical polyp (CIN), a precancerous stage of cervical cancer, at Hospital das Clínicas da USP (HC-USP).
“We were able to prove the concept in mice, and we are now validating the results in humans, following a small group of patients for six months to a year. We will move on to more comprehensive clinical trials to assess safety and immune system efficacy. Initial results are very encouraging,” she says. Bruna Portcia, a postdoctoral fellow at the International Institute for Schistosomiasis Control and first author of the study.
The immune system is applied to humans indirectly. A blood sample is taken from the patient, and in the laboratory, the dendritic cells are isolated and activated in the laboratory with an immunizing agent. After activation, the cells are returned to the patient in the form of an injection. This occurs when dendritic cells “teach” the immune system, through T lymphocytes, to recognize and eliminate cancerous or tumor precursor cells, known as neoplastic cells, in the cervix.
Due to the long regulatory path that must be followed for prevention to be conventionally applied to patients, the indirect method made it possible to implement this clinical proof of concept and validate the results achieved in the last two decades of research. The study was previously approved by the ethics committees for research with humans at the ICB and HC-USP and by the National Research Ethics Committee (Conep).
Pioneering technology
The immunizing agent is based on a recombinant protein that enables the activation of the immune system. “It is a vaccine that is capable of producing a highly specific response to a therapeutic target and, unlike methods such as chemotherapy and radiotherapy, does not affect healthy cells in the body. By doing so, cervical cancer can be eliminated with reduced toxicity,” says the researcher.
Building on the tests already done, the technology could be applied to combat other chronic or infectious diseases. “The possibilities are many. We could, for example, develop vaccines breast cancerAnd the Prostate cancertuberculosis, Lever Inflammationcovid-19, zika, and human immunodeficiency virus“, Highlights.
When applied in two doses, the immunomodulator can cure tumors in the early stages because at this time the best response of the body is achieved. “When cancer develops, often elusive mechanisms are created that override the immune system’s ability to eliminate it. In this case, linking the vaccine with other treatments could lead to good results.”
HPV and cancer
In 99.7% of cases, the cause of cervical cancer is the human papillomavirus. According to the World Health Organization (WHO), the disease, also known as cervical cancer, is the leading cause of death for women in Latin America and the Caribbean, causing 35,700 deaths each year. In Brazil, it is the fourth most common cancer in women, according to the National Cancer Institute (Inca).
Although the HPV vaccine has been part of the National Immunization Program of the Unified Health System (SUS) since 2014, diseases caused by the virus will continue to be a public health problem in Brazil due to low vaccination coverage. In 2021, for example, only 55% of the target population in Brazil was immunized, according to the Ministry of Health.
“When HPV infection persists and progresses to a tumor known as cervical intraepithelial neoplasia (CIN) and later to cervical cancer, forms of treatment include surgery, chemotherapy, radiotherapy or a combination of these treatments. Treatments have many effects. side effects that are detrimental to the quality of life of patients”, explains the researcher.