A new study by the University of Pittsburgh and the University of Pittsburgh Medical Centre (UPMC) in the US has revealed a new way to stimulate the immune system to enable immunotherapy to shrink or eradicate aggressive tumours.

By equipping oncolytic viruses, genetically modified viruses, with tumour-inhibiting genetic cargo, researchers found that it ‘warms up’ cold tumours in the immune system and helps immunotherapy tackle the tumour.

Oncolytic viruses were previously designed to directly eliminate cancer cells.

Researchers found that oncolytic viruses could stimulate the immune system, suggesting their potential use with other cancer therapies to remove the brakes on the immune system for T cells to recognise and combat tumours.

"Immune checkpoint inhibitors work only in ‘hot’ tumours, which have already been infiltrated by T cells," said Greg Delgoffe, associate professor of immunology at Pitt’s School of Medicine and director of the Tumor Microenvironment Center at UPMC Hillman Cancer Center.

Kristin DePeaux, a graduate student in Delgoffe’s lab, said: "We wanted to understand the mechanisms behind tumour resistance to these viruses to see what we can do to help patients."

After developing a head-and-neck squamous cell carcinoma (HNSCC) cell line that is sensitive to an oncolytic virus called vaccinia, researchers saw the tumours regress after a single dose.

Using an identical second cancer cell line that was resistant to vaccinia, they found that the resistance to vaccinia was driven by high levels of TGF-β, a signalling protein known to promote cancer growth.

Researchers engineered vaccinia to carry a gene encoding a TGF-β inhibitor, which resulted in a 50% clearance of tumours in mice with vaccinia-resistant HNSCC without causing autoimmune or toxicity-related side effects.

To see whether the modified viruses worked in highly aggressive forms of melanoma that are resistant to PD1 immune checkpoint inhibitors, researchers discovered that mice that received no treatment died within 24 days, and 20% of those that did receive the modified virus had complete clearance of the tumour.

Researchers also found that modified vaccinia combined with anti-PD1 caused 67% of tumours to completely clear and extended survival rates.

These results have the potential to pave the way for clinical trials combining oncolytic viruses with immunotherapy.

Delgoffe’s team has licensed their modified vaccinia virus to Kalivir Immunotherapeutics, which could soon be ready to test in human clinical trials as an adjuvant for immune checkpoint inhibitors for patients.

Reference：
https://www.pmlive.com/pharma_news/us_study_finds_potential_new_way_of_improving_immunotherapy_for_tumours_1496494