Rotavirus, known for causing gastroenteritis, has unexpectedly been transformed into a potential tool in the fight against stomach cancer, which is considered a public health problem in many countries. In Colombia alone, in 2020, the number of new cases was 8,214, ranking fourth in morbidity and ranking first in death rate, with 6,541 deaths in all age groups of men and women.
Specifically, the WT1-5 rotaviruses produced by directed experimental evolution (developed by virologist Carlos Guerrero and his team at the National University of Colombia (UNAL)) show great promise.
Through multiple passages in cultures of various human tumor cell lines (lung, breast, prostate, and gastric cancers, etc.), the virus was transformed into an agent capable of selectively and efficiently infecting and destroying tumor cells.
Its therapeutic potential is favored by its affinity for proteins that are increased or located on the cell membranes of these tumors, such as αVβ3 integrin, heat shock protein (Hsc 70) and disulfide isomerase (PDI) proteins.
The investigation involved six male patients aged 54 to 64 who had stomach cancer 5 years earlier and had their tumors surgically removed at the Lhasa Maritana University Hospital in Bogota.
None of these patients had received preoperative chemotherapy or radiotherapy, nor had multiple cancers in other organs at the same time or metachronously, that is, they had never been treated for the disease before.
Henry Sossa, Ph.D. in Biotechnology, Faculty of Dentistry, UNAL Bogota Campus, led a study using WT1-5 rotaviruses in oncolytic virotherapy (in which the drugs are engineered in the laboratory to destroy cancer cells). Gastric cancer, also known as gastric adenocarcinoma.
Henry Sossa, Ph.D. and Research Fellow in UNAL Biotechnology. (Photo: Henry Souza/UNAL)
“The virus has remarkable selectivity, specifically attacking tumor cells while minimizing the risk of damage to healthy cells,” said Dr. Sousa.
Like many countries, Colombia faces alarming rates of gastric cancer morbidity and mortality, and most patients have the disease undetected in its early stages, leading to tumors progressing to inoperable levels.
Traditional treatments, such as chemotherapy and radiation, often have side effects and limited survival.
The new findings offer hope of changing this reality. To this end, we tested gastric tumor tissue samples infected with WT1-5 rotavirus using an ex vivo infection model, ie, tumor tissue alive in infection medium.
The results showed that the virus multiplied efficiently in tumor cells from 12 hours after infection, and showed high infection within 24 hours.
In addition, rotavirus has also demonstrated its ability to spread to all layers of gastric tumors, inducing tissue necrosis within 48-60 hours.
“This surprising finding suggests that oncolytic virotherapy of WT1-5 rotavirus would be a rapid, effective and non-invasive adjuvant alternative therapy for patients with advanced cancer,” the experts noted.
Furthermore, this therapy has the potential to induce anti-tumor immune responses, improve treatment efficacy and reduce the chance of tumor recurrence.
This research was carried out in collaboration between UNAL and Samaritan University Hospital and required five years of hard work and effort in the field of oncology, for which this doctoral dissertation was awarded with distinction.
“The results validate the importance of the tumor explant model, bringing this innovative therapy closer to clinical trials in patients with unresectable gastric cancer. As a researcher, I believe this finding brings new benefits to those fighting advanced gastric cancer.” A New Hope”, concludes Sossa. (Source: UNAL Agency)