University of São Paulo: Therapeutic vaccine against cervical cancer has promising results in trials

Researchers at the Institute of Biomedical Sciences (ICB) at USP are developing a therapeutic vaccine that, in mice, was able to eliminate tumors associated with the human papillomavirus (HPV), the main causative agent of cervical cancer. Published in the International Journal of Biological Sciences , the study showed that, when associated with chemotherapy based on cisplatin, the vaccine induced a specific antitumor response capable of eliminating tumors at an advanced stage of development without showing toxicity. That is, it did not cause liver or kidney damage, nor did it induce weight loss in the animals. The researchers are now doing clinical proof of concept in humans.

The study is conducted by two ICB laboratories: Tumor Immunology, which is coordinated by Professor José Alexandre Marzagão Barbuto, and Vaccine Development, coordinated by Professor Luís Carlos de Souza Ferreira, in addition to the company ImunoTera Soluções Terapêuticas – a startup partner of the ICB founded by Bruna Porchia and by Luana Raposo Aps, collaborating researcher at the institute. The study also has the support of the Division of Gynecology at the Hospital das Clínicas (HC) at USP, through professors Edmund Chada Baracat and José Maria Soares Junior, and gynecologist Maricy Tacla.

Concept proof
The work was developed over the last few years in the rodent model of tumors associated with HPV-16 based on TC-1 cells, widely used by several groups in this research area. Currently, a clinical proof of concept is being conducted with patients diagnosed with high-grade cervical intraepithelial neoplasia (CIN), a stage prior to cervical cancer, at Hospital das Clínicas da USP (HC-USP).

“We were able to do the proof of concept in mice and now we are validating the results in humans, following a small group of patients for a period of six months to a year. The publication of the new results should be made in mid-2023 and then we will move on to more comprehensive clinical trials to assess the safety and efficacy of the immunizer. The initial results are very encouraging”, says Bruna Porchia, postdoctoral fellow at the ICB and first author of the study.

The application of the immunizer in humans is done indirectly. A blood sample is taken from the patient and, in the laboratory, the dendritic cells are isolated and activated in vitro with the immunizing agent. After activation, the cells are returned to the patient in the form of an injection. This is when dendritic cells “teach” the immune system, through T lymphocytes, to recognize and eliminate tumor cells or tumor precursors, known as neoplastic cells, in the cervix.

Due to the long regulatory path that must be followed until the immunizer is conventionally applied to patients, the indirect method made it possible to carry out 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 Human Beings of 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 capable of inducing a highly specific response to a therapeutic target and that, unlike methods such as chemotherapy and radiotherapy, does not affect healthy cells in the body. With this, it is possible to eliminate the neoplasms of the uterine cervix combined with a low toxicity”, says the researcher.

Based on the tests already carried out, the technology can be applied to combat other chronic or infectious diseases. “The possibilities are many. We can develop, for example, vaccines for breast cancer, prostate cancer, tuberculosis, hepatitis, covid-19, zika and HIV”, he highlights.

Applied in two doses, the immunizing agent can treat tumors in early stages because it is at this time that the body’s best response is achieved. “When a cancer evolves, evasion mechanisms are created that often overcome the immune system’s ability to eliminate it. In this case, the association of the vaccine with other therapies can bring good results.”

HPV and cancer
In 99.7% of cases, cervical cancer is caused by HPV. According to the World Health Organization (WHO), the disease, also known as cervical cancer, is the leading cause of death among 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 was immunized in Brazil, according to the Ministry of Health.

“When the HPV infection persists and progresses to a tumor known as Cervical Intraepithelial Neoplasia (CIN) and later to cervical cancer, the forms of treatment include surgery, chemotherapy, radiotherapy or combinations of these therapies. In addition to being invasive, these therapies bring many side effects that compromise the quality of life of patients”, explains the researcher.