Melanoma: preclinical success
A melanoma is a tumor growing from cells that produce melanin. Skin tumors are the most common oncological diseases in sunny Brazil and account for about 30% of all oncological pathology, the proportion of melanoma is 3% of neoplasms. However, it is most life-threatening due to the high probability of metastasis. The National Cancer Institute (INCA) estimates that about 8,400 cases of melanoma occur in Brazil each year. In 2019, this disease caused the death of almost two thousand people.
New cancer treatments developed in recent years include peptide-based chemotherapy. Peptides deserve more and more attention not only because they are able to bind to the membranes of cancer cells, but also because they have a low molecular weight, high bioavailability and low toxicity to normal tissue.
A research team from the Experimental Oncology Department of the Federal University of Sao Paulo (UNIFESP) in Brazil and the Brazilian biotechnology company Recepta Biopharma (ReceptaBio) demonstrated the effectiveness of the Rb4 peptide, which is derived from proteolipid protein 2 [PLP2], to combat the progression of cancer, especially melanoma. This molecule is promising for the treatment of drug-resistant tumors.
Preclinical in vitro and in vivo studies have shown that Rb4 causes necrosis of melanoma cancer cells in mice and suppresses the viability of human cancer cells. Under the influence of the experimental drug, cells lost the integrity of the plasma membrane, and mitochondria (energy–producing organelles) expanded even in the absence of chromatin condensation, a morphological sign of apoptosis. The researchers admit that they still do not understand what triggers this necrosis.
In mice, the peptide reduced lung metastasis and slowed the growth of subcutaneous melanoma. The results obtained indicate that Rb4 acts directly on tumors, inducing the expression of two apoptosis-related molecular patterns (DAMPs) that cause immunogenic death of melanoma cells.
The study was led by Luis Rodolfo Travassos, who died in 2020. He has published more than 230 articles in leading scientific journals, many of which are devoted to the study of peptides and peptidases (enzymes that break down proteins into peptides and eventually into individual amino acids) in infectious diseases and cancer.
In 2008, Travassos identified several sequences of bioactive peptides developed by ReceptaBio, including Rb4.
Another of the peptides found at that time, Rb9, is at a more advanced stage of research, several publications and patents have been devoted to it, but the work is still at the preclinical stage. In 2016, scientists described the structure of Rb9 and the mechanism of its action as an inhibitor of melanoma cells. A later paper published in 2020 showed that Rb9 acts as an immunomodulator and can be used to stop tumor progression.
Promising results
In a study of the antitumor effect of Rb4, the group found that the peptide interferes with the morphology and replication of B16F10-Nex2 melanoma cells cultured in the laboratory. In contrast to the control, the cells treated with Rb4 did not replicate and did not form clusters, losing their natural morphology after incubation for no more than 24 hours.
Melanoma cells before and after administration of the Rb4 peptide.
In addition, Rb4 reduced the number of metastatic nodes in the lungs in a model of syngenic melanoma containing tumor tissues of mice with the same genetic composition. This result was discovered after mice were injected intravenously with melanoma cells. They were alternately given five intraperitoneal peptide injections (300 micrograms per animal), delaying tumor growth for up to 40 days.
The survival rate of mice treated with Rb4 was more than 25% higher than that of control mice.
Article V.Maia et al. PLP2-derived peptide Rb4 triggers PARP-1-mediated necrotic death in murine melanoma cells published in the journal Scientific Reports.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert materials!: Peptide created by Brazilian group delays melanoma growth in animal trials.