Researchers from Barcelona have developed a new genetically engineered oncolytic virus, which can selectively infect and kill tumor cells.
Eneko Villanueva and colleagues from the IDIBAPS Biomedical Research Institute and the Institute for Research in Biomedicine (IRB Barcelona) have engineered a virus that infects tumor cells without affecting healthy tissues.
Their new cancer therapy approach is based on ‘oncolytic viruses’, which can differentiate between cancer cells and normal cells based on the expression of so called CPEB proteins.
CPEB is a family of four RNA binding proteins which can control the expression of hundreds of genes by binding to their RNA. In cancer, the balance of different CPEB proteins is often disturbed, contributing to malignant gene expression of these cells.
The researchers have shown that many cancer cells overexpress CPEB4, which seems to be necessary for tumor growth. On the other hand, the cancer cells loose the expression of CPEB1, which is highly expressed in normal tissues.
We have taken advantage of this imbalance to make a virus that only attacks cells with high levels of CPEB4 and low CPEB1. That means that it only affects tumor cells, ignoring the healthy tissues,” says Méndez, who co-lead the study.
To make the viruses specific towards high CPEB4/ low CPEB1, the researchers have inserted sequences into the genome of an adenovirus, which recognize CPEB proteins. With this strategy, they achieved attenuated viral activity in normal cells, while in tumor cells the virus potency was maintained or even increased. Once the virus infects a cancer cell, it will destroy the cell and release even more viral particles.
Oncolytic viruses make up a very promising therapeutic strategy and there are several biotechs developing such viruses for cancer therapy. Recently, Brystol-Myers Squibb signed a €850M ($886M) deal for the exclusive worldwide rights of NG-348, a next-generation oncolytic virus developed by PsiOxus. The virus is currently in preclinical development.
PsiOxus’ lead viral candidate Enadenotucirev, which selectively kills cancer cells and at the same time triggers the immune system, is already in Phase I clinical trials. Amgen’s IMLYGIC was the first oncolytic virus to be approved by the FDA in 2015 for the treatment of refractory melanoma.
Although there are already some viruses in the pipeline, the new virus developed by the researchers in Barcelona may be a promising addition to this young and developing market.
Images via shutterstock.com / photo5963_shutter and Amgen