Previous work by a team of researchers led by Steven N. Fiering, PhD, Immunology and Cancer Immunotherapy researcher at Dartmouth's and Dartmouth-Hitchcock's Norris Cotton Cancer Center and Nicole Steinmetz, PhD, Jacobs School of Engineering and Moores Cancer Center, University of California San Diego, showed that a plant virus that does not infect mammals, cowpea mosaic plant virus (CPMV), when injected into cancerous tumours, strongly stimulated the immune system to attack and often eliminate the tumour.

However, very little was understood about immune recognition of plant viruses and how and why CPMV is exceptionally immuno-stimulating.

In a new study, the team identifies just how CPMV is recognised by the immune system, opening the door for CPMV to be pursued as a new biological drug for treatment of cancer.

CPMV is recognised by the immune system as a pathogen--any infectious agent that can cause disease--through a family of receptors on immune cells called toll-like receptors.

Toll-like receptors recognise molecules that signal the invasion of a pathogen and send a warning signal to the immune cells to mobilise to attack the pathogen.

When tumours are injected with CPMV, the immune system activates and attacks the tumours by way of this pathogen pattern recognition. "The recognition of CPMV by toll-like receptors illustrates how these receptors are quite flexible and recognise many more molecular patterns than immunologists previously knew," says Fiering.

During the immune stimulation process, the immune cells release proteins that signal and activate other immune cells, known as cytokines.

The team's study, "Cowpea mosaic virus stimulates antitumour immunity through recognition by multiple MYD88-dependent toll-like receptors," newly published in Biomaterials, identifies the three toll-like receptors that recognise CPMV.

The paper also highlights the importance of a particular cytokine, "interferon alpha," for strong anti-tumour impact when used as an in situ vaccine to treat cancer.

In situ vaccination, in which tumours are directly treated with immune stimulating reagents, have powerful potential to improve cancer immunotherapy in a safe and inexpensive manner.

"In situ vaccination has made contributions already to cancer treatment. CPMV is an excellent reagent that may soon be used to help patients in the same manner," says Fiering.

"The in situ vaccination treatment of a tumour by CPMV can stimulate the immune system to also attack distant metastatic tumours that have not been treated."

Source: Dartmouth-Hitchcock Medical Center

Image: UCSD