Researchers from the National Center for Research in Energy and Materials (CNPEM), in Campinas (SP), managed to modify the structure of a virus and implement a technology allied in the fight against prostate cancer. The study points to a less invasive way for tumors to be identified and signaled, and subsequently attacked by the body’s defense cells.
The technique is innovative and was published in the American scientific journal Molecular Therapy Oncolytics. Results in tests carried out with animal models ensured 90% inhibition of cancer cells.
“The perspective is that we will be able to transport it to humans. I believe that in about 5 years we will reach a result equal to what we had for animals”, he said in an interview with g1 researcher Márcio Chaim Bajgelman.
The strategy is to use virus-like particles known as VLPs and popularized in the dissemination of techniques for the development of vaccines against Covid-19.
In the strategy of the researchers from Campinas, the “carcass” of a particle with virus characteristics receives an envelope “decorated” with proteins that manage to bind to the markers existing in prostate cancer cells, PSMA.
“We developed a nanoparticle that we decorated with ligands. One of the ligands will direct the particle to the tumor site [local específico onde o câncer está]. If we administer this particle into the bloodstream, it will find the tumor site,” said Chaim.
“Prostate cancer can metastasize, in which case our particle will also be able to find tumor foci in other locations,” he added.
Overstimulation of defense cells
This envelope also has molecules that stimulate the immune system, warning that tumors can be attacked and preventing the cancer from being able to “cheat” the defense cells, as in some cases of autoimmune diseases.
“Cancer cells will present markers on the surface, little ‘flags’. The immune system cells, such as lymphocytes, will find the one that is waving. Everyone has this repertoire of millions of lymphocytes in the body. The problem is that this recognition alone is not enough, it needs a push. The nanoparticle will find this marker and give a second signal to the lymphocyte, which will inform that it needs to be activated now”
“[No futuro] we will be able to produce this in a very large volume, execute the mechanism with a process of purification, formulation, and in the end we would have a drug”.
Images from the study on nanoparticles against prostate cancer show adherence of proteins in VLPs on the cell surface — Photo: Reproduction/CNPEM
Therapy with these innovative biomarkers also offers hope in terms of reducing side effects in people undergoing treatment.
“Today, people who use chemotherapy have many adverse reactions, hair loss, problems in the gastric mucosa. There is a problem for the patient. The more the chemo increases, the more the patient wears out. There is a balance between killing the cancer cell and not kill the patient with the chemotherapy”.
With the body healthier to go through the cancer, the chances of cure also increase, according to Chaim. The use of biological nanoparticles can be combined, in the future, with existing therapies, such as chemo, radio and immunotherapies.
“Cancer comes back because it has cells that escape therapy and the immune system, and form a tumor again. When you have other strategies available, such as immunotherapy, in combination with other strategies, you can increase the efficiency of the treatment.”
How have the tests been so far?
- Work began in 2012, with the development of the concept, and in 2015 the clinical trials began.
- The protocols were submitted and approved by an ethics committee.
- Lymphocytes isolated from mice were used to receive PSMA human prostate cancer tumor cells.
- Markers were placed on the tumor cells to see if they would be eliminated.
- They built the nanoparticles with combined immunomodulators, with greater potency to eliminate cancer.
- They applied the strategy for defense cells, T lymphocytes, not to transform into regulatory cells, which could give rise to an autoimmune response.
- They managed to make the defense cell more potent, but efficient and aggressive, to eliminate cancer.
- In animals, the tumors grew and were treated with nanoparticle technology developed by CNPEM. There was a 90% inhibition.
- The study with the results was published in the American scientific journal on March 24.
Researcher at CNPEM, in Campinas, Márcio Chaim Bajgelman — Photo: Giancarlo Giannelli/CNPEM
The study, financed with funds from the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp), had good results in vitro and also in mice. CNPEM is an organization supervised by the Ministry of Science, Technology and Innovation (MCTI) and the innovative technology developed is national.
The next step is to create a reality more similar to that of humans, but still in animals, to track the results within the next five years.
The tests will be carried out in human cell culture and humanized animal models will also be used, according to the researcher.
“Our particles will have to have ligands to stimulate human lymphocytes, which have different receptors. We have to have human ligands. The first proof of concept is in the culture plate. The second test is to verify in the animal if it eliminates human tumors. animals in the laboratory”, explained Márcio Chaim, detailing that this is the usual process for drug development.
“I imagine that in 5 years we will already have humanized particles working in the humanized model and clinical tests carried out”, he added.