Abstract
“Bug as drug” is a concept recognized over a century ago and has gained significant research attention recently for fighting diseases such as immune disorders and others. Bacteria and viruses are constantly studied for this purpose, but the use of parasitic organisms is still rare. Recently, we found that Toxoplasma gondii mutants lacking two lactate dehydrogenases (ME49 Δldh1-Δldh2) were avirulent in mice but able to stimulate high levels of Th1 immunity. This outcome prompted us to determine whether Δldh mutants also displayed antitumor activities. Using a mouse melanoma model, we showed that intratumoral administration of Δldh1-Δldh2 repressed the growth of established tumors and helped to inhibit lethal tumor development in the mice. The sera of parasite-treated mice had high levels of TNF-α and INF-γ, which likely contributed to the tumor-repressing activity. We also found that chronic Toxoplasma infection, which is common in animals and humans, also led to antitumor activity. In addition, pre-existing chronic infections did not affect the antitumor efficiency of the Δldh1-Δldh2 mutant. Together, these results suggest that the attenuated T. gondii mutant Δldh1-Δldh2 has the potential to be a good antitumor therapy and provide new insights into the development of novel tumor therapeutics.
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Acknowledgements
The authors want to thank colleagues from the College of Veterinary Medicine, Huazhong Agricultural University, for their suggestions for this study.
Funding
This work was supported by the National Key Research and Development Program of China (grant no. 2017YFD0501304).
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BS designed the research. All authors contributed to data acquisition and analyses. YL, YZ, and BS wrote the manuscript. All authors have approved the submitted paper.
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All animal experiments, as well as the procedures for animal care and treatments, were approved by the ethics committee of Huazhong Agricultural University (Permit # HZAUMO-2017–045). All institutional and governmental regulations concerning the use of experimental animals were followed.
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Section Editor: Xing-Quan ZHU
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Li, Y., Zhang, Y., Xia, N. et al. Antitumor effects of a Toxoplasma mutant lacking lactate dehydrogenases. Parasitol Res 120, 3335–3339 (2021). https://doi.org/10.1007/s00436-021-07283-9
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DOI: https://doi.org/10.1007/s00436-021-07283-9