Common parasite could be latest cancer-fighting tool

Schematic 3D model of Toxoplasma gondii inside a host cell.
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 ill health in immunocompromised humans, could potentially be used to treat various types of tumours.

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

Toxoplasma gondii has been reported in nearly one-third of the world’s human population, and has been isolated in 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 sensitise cold tumours – tumours that are not likely to trigger a strong immune response by the body – to immune checkpoint blockade therapy. Scientists leading the study believe that this finding could have broader therapeutic implications for many types of cancers.

They managed to ‘tame’ Toxoplasma gondii , which lives inside the cells of its host and secretes many proteins to counter the host’s immune defences and to facilitate their own invasion and colonisation of the host cells. The researchers first built a Toxoplasma 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.

The researchers have shown that direct injection with this mutant parasite in solid tumours, induces inflammatory responses in the injected tumours and even in tumours located in a distant location in the mouse body. They have also shown that this treatment approach has made tumours more responsive to treatment with immune checkpoint inhibitor.

This dual treatment significantly extended the survival of mice and reduced tumour growth in mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma.

Dr Hany Elsheikha, 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 Toxoplasma gondii in the treatment of certain tumours in mice models has been previously reported. What makes this study different is the confirmation that intratumoral injection with mutant Toxoplasma gondii strain boosts antitumor immunity and the effectiveness of checkpoint inhibition therapy.

“These are significant findings and are relevant to future tumour therapy. The marked reduction in tumour 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.”

Synergy between Toxoplasma gondii type I ΔGRA17 immunotherapy and PD-L1 checkpoint inhibition triggers the 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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