Treatment based on the combination of immunotherapy and chemotherapy reduced the tumor by 80% in animals
Pancreatic cancer, one of the most aggressive, is responsible for around 5% of deaths from tumors worldwide. Depending on the type and time taken for diagnosis, patient survival is very low and therapeutic alternatives are scarce, due to metastases and functional impairment of other organs, particularly the liver. Concerned by the aggressiveness of this tumor, Professor Wagner José Fávaro, from the Department of Structural and Functional Biology at the Institute of Biology (IB) at Unicamp, guided research aimed at characterizing the histopathology and progression of the disease, as well as comparing the effects of immunotherapy associated with chemotherapy on her.
The study verifying the role of immunotherapy, which uses the individual's immune system to combat the disease, and the action of chemotherapy in the distribution of tumor cells, was carried out on 50 laboratory animals. The results showed that the combination of immunotherapy and chemotherapy for the treatment of pancreatic cancer led to an 80% reduction in the tumor in these animals, potentially contributing to the development of a new therapeutic modality for this disease. The work culminated in the master's thesis by Mariana Martins dos Santos (Capes scholarship), which had the collaboration at the scientific initiation level of Maísa Massafera (Fapesp scholarship) and the co-supervision of professor Patrick Vianna Garcia, also from IB.
Wagner Fávaro explains that in cases of pancreatic cancer in which surgical intervention is not possible, the only option left is chemotherapy, which does not provide a response for 40% to 60% of patients, or requires the application of a combination of chemotherapy drugs. However, as this tumor has the ability to spread quickly to other organs, and the liver is its first target, hepatic impairment greatly restricts the use of such medications.
Therefore, the concern in this research is to first verify the possibility of fighting the tumor by activating the individual's immune system. A drug was used that activates immune system receptors and creates potential conditions for attacking the tumor. Such therapy, which has already proven to be effective for other tumors, had not yet been studied for pancreatic cancer. It should be added that, despite the many drugs developed to act on cancer, few are effective for this organ.
The work
Given this situation, Fávaro asked himself some questions: would the activation of the immune system determine the attack on pancreatic tumor cells in a way that would lead to the patient's improvement?; Could the combination of immunotherapy and chemotherapy determine more effective results in attacking this type of tumor?; Or, even, could this association make it possible, when necessary, to reduce the dose of chemotherapy, minimizing its toxic effect, which manifests itself in the destruction of even healthy cells?
Seeking to answer these questions, the immunomodulator P-MAPA (acronym in English for polymeric aggregate of magnesium ammonium phospholinoleate-palmitoleate protein) was used, a product originating from the fungus Aspergillus oryzae, a substance not yet commercialized, and the chemotherapy gemcitabine, already quite well known. “Our surprise was that pancreatic tumors are sensitive to local activation of the immune system and this response is even slightly superior and more effective than chemotherapy, but not sufficient. But when associated with chemotherapy, it leads to an 80% reduction in tumors induced in the animals studied.”
The explanation, adds the researcher, is that the immunomodulator, upon reaching the tumor tissue, triggers a more exacerbated inflammatory response against the tumor cells, the body's natural mechanism for attacking bodies that are foreign to it. In addition to activating the tissue's immune system capable of attacking the tumor, the immunomodulator reduces the blood vessels that nourish it. At the same time, chemotherapy, which has another mechanism, destroys diseased cells and stops the production of new tumor cells. This therapeutic association proved to be very effective, reducing and stopping cancer. For him, the work opens up perspectives for the application of this therapeutic association in humans, making it possible to prolong and improve the patient's quality of life.
According to the IB professor, the next planned step involves survival testing, still on animals, in order to determine the time it takes for the tumor to reappear after stopping the medication, which will also serve to establish the period in which that it needs to be applied. There is still a need to test the therapy in other animals with similar characteristics.
Multidisciplinary context
Anatomist Wagner José Fávaro heads the IB's Urogenital Carcinogenesis and Immunotherapy Laboratory, which began working with prostate and urinary bladder tumors and later expanded studies to ovarian, breast, colorectal and pancreatic cancers. He credits this evolution and breadth to partnerships that gave the research multidisciplinary dimensions. Among them, the professor mentions the joint work with the urooncology and surgery sectors of the Hospital de Clínicas (HC) at Unicamp. His teaching work also extends to the Faculty of Medical Sciences (FCM), teaching undergraduate classes and supervising students in the Postgraduate Program in Surgical Sciences – where this dissertation on pancreatic cancer was actually developed.
Another contribution that the researcher considers fundamental comes from the partnership with the Solid State Chemistry Laboratory (LQES) and the Biological Chemistry Laboratory (LQB) coordinated, respectively, by professors Oswaldo Luiz Alves and Nelson Durán, both from the Chemistry Institute ( IQ) from Unicamp. As of 2013, these laboratories merged into the Laboratory of Nanostructure Synthesis and Interaction with Biosystems (NanoBioss). Thus, an associated reference laboratory of the National System of Nanotechnology Laboratories (SisNano) emerged, financed by the Ministry of Science, Technology and Innovation (MCTI), which brings together the greatest experts in this area in the country.
The partnership with IQ professionals has led to the development, for biological application, of new drugs, their syntheses and characterizations, which has enabled the use of new therapeutic associations for tumors. The researcher is keen to emphasize that “these partnerships are always focused on the needs of society, reciprocating in the form of knowledge what the country spends on its universities”.