Common parasite could be the latest tool in the fight against cancer

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Schematic 3D model of Toxoplasma gondii inside a host cell. Image: Yu-Chao, Elsheikha et al

Scientists have discovered that the deadly parasite Toxoplasma gondii, which causes toxoplasmosis in warm-blooded mammals, including equines, and poor health in immunocompromised humans, could potentially be used to treat various types of tumors.

The research, published in the Journal for ImmunoTherapy Cancer, was carried out by experts from the University of Nottingham, the University of Ningbo and the Agricultural University of Shanxi in China.

Toxoplasma gondii has been reported in almost a third of the world’s human population and has been isolated from horses in several countries. In a recent study in Israel, antibodies against T. gondii were found in 94% of the donkeys tested.

The researchers found that Toxoplasma gondii, a single-celled opportunistic protozoan, is able to sensitize cold tumors – tumors that are not likely to trigger a strong immune response from the body – to immune checkpoint blocking therapy. Scientists leading the study believe the discovery could have broader therapeutic implications for many types of cancer.

They managed to “tame” Toxoplasma gondii , which lives inside its host’s cells and secretes numerous proteins to counter the host’s immune defenses and to facilitate their own invasion and colonization of host cells. The researchers first built a Toxoplasm gondii mutant strain with limited ability to grow, in cultured cells or to cause disease in mice, but which at the same time is capable of manipulating the host’s immune system.

Researchers have shown that direct injection of this mutant parasite into solid tumors induces inflammatory responses in injected tumors and even in tumors located remotely in the body of mice. They also showed that this treatment approach made tumors more responsive to treatment with an immune checkpoint inhibitor.

This dual treatment dramatically prolonged mouse survival and reduced tumor growth in mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma.

Dr Hany Elsheikha, associate professor in the School of Medicine and Veterinary Sciences at the University of Nottingham, and one of the lead authors of the study, said: “The use of a mutant version of Toxoplasma gondii in the treatment of certain tumors in mouse models has already been reported. What makes this study different is the confirmation that intratumoral injection of mutants Toxoplasma gondii The strain increases anti-tumor immunity and the effectiveness of checkpoint inhibition therapy.

“These are important and relevant findings for future anti-tumor therapy. The marked reduction in tumor size and the significant improvement in survival of mice that received this new combination therapy are promising but should be interpreted with caution as more research is needed.

Synergy between Toxoplasma gondii type I ΔGRA17 immunotherapy and PD-L1 checkpoint inhibition triggers regression of targeted and distal tumors. Yu-Chao Zhu, Hany M Elsheikha, Jian-Hua Wang, Shuai Fang, Jun-Jun He, Xing-Quan Zhu and Jia Chen. Journal for ImmunoTherapy Cancer.

The study, published under a Creative Commons License, can be read here.


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