State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.
Key Laboratory of Preventive Medicine in Hubei Province, Huazhong Agricultural University, Wuhan, China.
Parasitol Res. 2021 Sep;120(9):3335-3339. doi: 10.1007/s00436-021-07283-9. Epub 2021 Aug 18.
"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.
"虫为药"是一个一个多世纪前就被认可的概念，最近在治疗免疫紊乱等疾病方面受到了广泛关注。为此，人们一直在研究细菌和病毒，但寄生虫的应用仍然很少。最近，我们发现缺失两种乳酸脱氢酶（ME49Δldh1-Δldh2）的刚地弓形虫突变体在小鼠中无毒性，但能够刺激高水平的 Th1 免疫。这一结果促使我们确定 Δldh 突变体是否也具有抗肿瘤活性。我们使用小鼠黑色素瘤模型表明，肿瘤内给予 Δldh1-Δldh2 可抑制已建立的肿瘤生长，并有助于抑制小鼠致命性肿瘤的发展。寄生虫处理过的小鼠的血清中 TNF-α 和 INF-γ 水平较高，这可能有助于抑制肿瘤生长。我们还发现，在动物和人类中很常见的慢性弓形虫感染也具有抗肿瘤活性。此外，先前存在的慢性感染不会影响 Δldh1-Δldh2 突变体的抗肿瘤效率。总之，这些结果表明，减毒的刚地弓形虫突变体 Δldh1-Δldh2 具有成为一种良好的抗肿瘤治疗方法的潜力，并为新型肿瘤治疗药物的开发提供了新的思路。
