Toxoplasma gondii is one of the world’s most common parasites. It is a protozoan parasite that infects most species of warm-blooded animals, including humans, and causes the disease toxoplasmosis. Toxoplasmosis may cause flu-like symptoms in some people, but most people affected never develop signs nor symptoms. However, it may cause serious complications in pregnant women and immunocompromised patients. Now, a mouse study by researchers from the University of Nottingham, Ningbo University, and Shanxi Agricultural University in China demonstrates the parasite may be able to sensitize cold tumors.
Their findings are published in the Journal for ImmunoTherapy Cancer, in a paper titled, “Synergy between Toxoplasma gondii type I ΔGRA17 immunotherapy and PD-L1 checkpoint inhibition triggers the regression of targeted and distal tumors.”
“In this study, we hypothesize that the ability of the protozoan T. gondii to modulate immune response within the tumor might improve the therapeutic effect of immune checkpoint blockade,” the researchers wrote. “We examined the synergetic therapeutic activity of attenuated T. gondii RH ΔGRA17 strain and programmed death ligand-1 (PD-L1) treatment on both targeted and distal tumors in mice.”
The team of researchers first built a T. gondii mutant strain with a limited ability to grow, in cultured cells or to cause disease in mice, but at the same time is able to manipulate the host immune system.
Direct injection with this mutant parasite in solid tumors, induces inflammatory responses in the injected tumors and even in tumors located in a distant location in the mouse body. The researchers also demonstrated their treatment approach has made tumors more responsive to treatment with immune checkpoint inhibitors. The combination therapy extended the survival of mice and reduced tumor growth in mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma.
Hany Elsheikha, PhD, associate professor in the School of Veterinary Medicine and Science at the University of Nottingham, and one of the lead authors of the study, said: “The use of a mutant version of T. gondii in the treatment of certain tumors in mice models has been previously reported. What makes this study different is the confirmation that intratumoral injection with mutant T. gondii strain boosts antitumor immunity and the effectiveness of checkpoint inhibition therapy.
“These are significant findings and are relevant to future tumor therapy. The marked reduction in tumor size and the significant improvement in the survival of mice that received this novel combinational therapy is promising but should be interpreted with caution as further research is needed.”
