Oncolytic Virus Shows Promise in Colon Cancer Treatment

An oncolytic virus developed by researchers at City of Hope shows potential for the treatment of colon cancer, priming the immune system to eliminate tumors that are typically resistant to treatment, a study published in Molecular Cancer Therapeutics found.¹

In preclinical research done on mouse models, the oncolytic virus CF33 paired with a PD-L1 checkpoint inhibitor targeted solid tumors that would otherwise resist immunotherapies. The virus seemed to increase PD-L1 expression in tumor cells, killing them in a way that also prompted a spike in activated immune cells.

Treating cancer with a virus is a cutting-edge approach, and despite the way viruses are typically perceived by public—after all, we are in the middle of a pandemic because of one—oncolytic viruses are safe, unless you happen to be a cancer cell.

“Oncolytic viruses are naturally occurring or genetically engineered viruses that target cancer cells for infection and destruction, leaving normal cells unharmed. Oncolytic viruses can destroy cancer cells by direct infection and killing; they can also help train the immune system to see and target cancer cells,” Susanne Warner, MD, a surgical oncologist at City of Hope and senior author of the study, told The American Journal of Managed Care® (AJMC®).

So far, only one oncolytic virus, talimogene laherparepvec (T-VEC; tradename Imlygic), is FDA approved for local treatment of unresectable cutaneous, subcutaneous, and nodal lesions recurring after initial surgery in melanoma.² 

Importantly, viruses can make “cold,” treatment-resistant tumors “hot,” Warner said. “This means taking an area where not a lot of immune cells can get to and creating a more inflamed environment that opens the door and attracts and activates more immune cells. This process effectively primes tumors for other immunotherapies like immune checkpoint inhibitors to work better.”

To test the efficacy of the CF33 virus, City of Hope researchers separated mice into 4 cohorts. A control group received no treatment, a second group received an anti-PD-L1, the third cohort received CF33 alone, and a fourth received a combination of CF33 and anti-PD-L1. The combination treatment was most effective, suggesting that CF33 could be an effective primer for immune checkpoint inhibitors.

Another key finding was that the treatment increased CD8+ T cells, which remember diseases and will attack them if they are reintroduced later. In the study, mice that had complete tumor regression seemed immune to tumor regrowth.

“We were excited to show that mice cured of their tumors were unable to regrow tumors even when they received the tumor cells again. We definitively showed that this was due to a memory-based immune reaction against cancer cells,” Warner said. “We did this by challenging those same cured mice with a different type of tumor to which they had not yet been exposed. Those new tumors readily grew while the tumors from which the mice were cured of did not.”

She added that when the team assessed the strength of T cell activation against tumor cells under different treatment conditions, they found that T cells from cured mice were dramatically more activated when they saw an infected cancer cell again compared with those in control groups.

“We are studying our findings in models of other cancers right now,” Warner said. “Based on previous findings, we suspect that what we have seen with T cell priming in colon cancer models will hold true across other solid tumor types.”

The CF33 virus can also be tracked with non-invasive PET scanning, noted a press release from City of Hope.³ This means doctors could potentially inject someone with CF33 and watch the virus move through their system as it targets cancer cells. Simultaneously administering therapy and diagnosing patients is a developing field called theranostic precision medicine.

CF33 could prove game-changing in the treatment of solid tumors, and a clinical trial to test the safety and efficacy of the virus in humans is expected to start in 2021.

“The important thing our work points out is there is still so much to learn about exactly how viruses interact with the immune system,” Warner said. “More importantly, since virally infected cells in vitro were able to re-ignite activation signals in T cells from cured mice, this speaks to the importance of serial dosing strategies moving forward.”

References

1. Kim S, Park AK, Chaurasiya S, et al. Recombinant Orthopoxvirus Primes Colon Cancer for Checkpoint Inhibitor and Cross-Primes T Cells for Antitumor and Antiviral Immunity. Mol Cancer Ther. Published online December 1, 2020. Accessed December 1, 2020. doi:10.1158/1535-7163.MCT-20-0405

2. IMLYGIC (talimogene laherparepvec). US Food & Drug Administration. Updated December 13, 2019. Accessed December 1, 2020. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/imlygic-talimogene-laherparepvec

3. City of Hope has developed a cancer-killing virus that activates immune system, helps eliminate colon cancer. News release. City of Hope; December 1, 2020. Accessed December 1, 2020. https://www.cityofhope.org/news/cancer-killing-virus-helps-eliminate-colon-cancer