Enhanced nutrition for lymphocytes

Modified microbes feed anti-cancer T cells

Kirill Stasevich, Science and Life (nkj.ru )

T-lymphocytes should destroy malignant cells, but they do not always succeed. One of the reasons is that there are few necessary substances in the tumor, where T—lymphocytes should work. Like any other, T-lymphocytes need certain compounds, without which they perform their functions poorly. One of the most important items in the "menu" is the amino acid L—arginine (the letter L means one of the isomeric forms of the amino acid). L-Arginine helps T cells live longer, stimulates processes related to immune memory, and also stimulates their anti-cancer properties. But when the T-lymphocyte approaches the tumor and sinks into it, the level of arginine around it will drop sharply.

At the same time, it is still unclear how to supply T cells with the necessary L-arginine. If you give it in the form of tablets or powder, then the patient should absorb huge amounts of the drug daily, and it is not a fact that such doses of L-arginine will not provoke various unpleasant side effects. It is possible to inject L-arginine directly into the tumor only when it is not too deep, and besides, most of the amino acid will leak from the tumor into other tissues fairly quickly, and the effect will be blurred.

The staff of the University of Lugano offers an original way to supply anti-cancer T cells with L-arginine. The metabolic features of cancer cells are such that they produce a lot of ammonia (which exists in solution in the form of ammonium ion NH4+). This ammonia can be converted into L-arginine on the spot. Its synthesis can be entrusted to modified bacteria of E. coli, which has the necessary genes. But E. coli also has a gene that suppresses the synthesis of L-arginine. It needs to be turned off, but the gene that helps synthesize L-arginine needs to be modified so that it works as actively as possible and does not turn off even when there is a lot of L-arginine.

But why, in fact, bacteria? The fact is that bacteria like malignant tumors. Bacteria live in all malignant tumors, moreover, they harm tumors, attracting the attention of the immune system to them. And since bacteria like to accumulate where there are cancer cells, researchers have long had the idea that they can be used to fight cancer. Bacteria synthesizing L-arginine is one of the new experimental methods of anti—cancer therapy.

An article in Nature (Canale et al., Metabolic modulation of tumours with engineered bacteria for immunotherapy) states that arginine-synthesizing bacteria stimulated an immune attack on the tumor in mice: there were more of those T-lymphocytes that kill cancer cells, and fewer of those T-lymphocytes that suppress the immune response (such cells are also needed, but they turn out to be inappropriate in the tumor). The anti-cancer activity of the immune system can be spurred with the help of special immunotherapy. In one experiment, the researchers combined arginine bacteria with such immunotherapy and the effect was stronger than when bacteria and immunotherapy were used separately. The bacteria acted regardless of whether the bacterial drug was given to mice by mouth or injected directly into the tumor. They worked both in mice with colon cancer and in mice with a type of melanoma. The mice did not have any poisoning associated with bacteria, but the animals steadily lost weight after bacteriotherapy.

Further research will show how effective and safe this method of cancer treatment will be for people. Perhaps, for clinical purposes, it is worth embedding some kind of self-destruction mechanism in such bacteria, so that, having worked for the benefit of the patient, they themselves quietly leave the scene.

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