Chemo and ONCOS-102 Work Together to Fight Mesothelioma

A new drug might turn out to be a viable treatment against mesothelioma. ONCOS-102 is a dual-targeting, chimeric oncolytic adenovirus.

The new drug is being tested in Europe. In a recently completed preclinical trial, it was shown to exhibit anti-tumor activity. Specifically, it triggered immunogenic cell death in mesothelioma specimens.

Researchers from the University of Helsinki in Finland and from the National Institute of Public Health in Warsaw, Poland, wrote about this in the online edition of the International Journal of Cancer.

They explained that the preclinical trial provided insights as to what ONCOS-102 could do alone and also with mesothelioma chemotherapy consisting of pemetrexed and cisplatin.

Interestingly, chemotherapy by itself wasn’t notably effective. ONCOS-102 on the other hand did manage to slow tumor growth.

The real excitement emerged when ONCOS-102 and chemotherapy were combined. Together they exerted a synergistic effect against mesothelioma samples contained in a xenograft BALB/c model.

The researchers said these results justify plans for conducting a clinical trial with humans later this year.

ONCOS-102 Actives CD8+ T cells to Fight Mesothelioma

ONCOS-102 is the creation of a Finnish firm called Targovax. The company focuses on clinical stage, targeted immunotherapy treatments for mesothelioma and other cancers.

ONCOS-102 is an engineered human serotype 5 adenovirus. The engineering is intended to optimize its ability to make the body’s immune system unleash anti-tumor T cell responses.

The company says ONCOS-102 helps the immune system regain something mesothelioma takes away — the ability to activate CD8+ T cells. CD8+ T cells are cells capable of recognizing and attacking mesothelioma cells.

Targovax explains that it chose to design its immunotherapy drug around an adenovirus because adenoviruses are good activators of CD8+ T cells.

In this case, the adenovirus is even better than it would normally be when it comes to CD8+ activation, thanks to special engineering.

This engineering includes a change to the adenovirus’s knob protein. Targovax has swapped it with one derived from a different adenovirus. The knob protein enables an adenovirus to find and penetrate a healthy host cell.

The replacement knob protein makes it easier for ONCOS-102 to insert itself into a mesothelioma tumor cell once it locates one, the company says.

Targovax also modified one of the adenovirus’s genes. The gene in question instructs the virus to replicate after entering a host cell. Targovax’s modification allows ONCOS-102 to replicate only within mesothelioma cells.

How This New Drug Works Against Mesothelioma

There is a protein the body produces when it needs the immune system to swing into gear. That protein is called granulocyte macrophage colony-stimulating factor, or GM-CSF.

ONCOS-102 is engineered so that it expresses GM-CSF once a mesothelioma cell has been penetrated. Expressing GM-CSF is like a scout sending a signal back to headquarters. It tells the immune system to gird for battle and send a task force of CD8+ T cells to these coordinates.

The actual mechanism of action looks like this. First, the ONCOS-102 particles infect tumor cells. This leads to immunogenic tumor cell death. That, in turn, releases tumor antigens plus new ONCOS-102 particles.

All of that along with production of the co-stimulatory molecule GM-CSF “attracts antigen-presenting cells to the tumor,” the company explains.

“These cells take up tumor antigens and also ONCOS-102 antigens,” Targovax adds. “Antigen-presenting cells — such as dendritic cells — migrate to lymph nodes with the antigens.”

The company says these antigens are then presented to the T cells, causing them to activate. Activation allows them to recognize cells expressing those antigens. Recognition means the T cells know where to attack.

The title of the article is “Synergistic anti-tumor efficacy of immunogenic adenovirus ONCOS-102 (Ad5/3-D24-GM-CSF) and standard of care chemotherapy in preclinical mesothelioma model”