Nat Biotechnol: Scientists are expected to develop a new potential anti-cancer drug

The therapeutic potential of recombinant cytokines has always been limited by the serious side effects of systemic administration; Recently, a study entitled "A split, conditionally active mimetic of IL-2 reduces the toxicity of systemic cytokine therapy" published in the international journal Nature Biotechnology, scientists from the University of Washington School of Medicine and other institutions have shown that When an experimental cancer drug is split in two, the molecule may become safer and more effective
.

Researchers have been looking for new ways to improve a potential cancer drug called Neo-2/15, a protein drug developed to mimic the function of interleukin-2 (IL-2), a natural molecule that boosts the body's immune cells' ability
to fight off infection and cancer.
When IL-2 is used to treat certain cancers, this systemic cytokine therapy may cause toxic side effects in patients, so the researchers designed Neo-2/15 to be a better version of IL-2, that is, one in which the side effects can be reduced
.

Scientists are expected to develop a new potential anti-cancer drug
.

Image source: Nature Biotechnology (2022).
DOI:10.
1038/s41587-022-01510-z

To further refine Neo-2/15, the researchers dissected the molecule, and when it was cut in the right way, the resulting drug fragment neither showed beneficial activity nor unwanted side effects; When these fragments are recombined with molecules on the surface of cancer cells, the activity of the drug is restored
.
The researchers tested the novel split-drug approach in cancerous mice, and as expected, a single drug fragment did not exhibit any anti-tumor activity, but when these fragments were administered at the correct dose, some animals achieved complete tumor remission without exhibiting any toxic side effects, which was not the case in mice treated with IL-2 or intact Neo-2/15.
Although these drugs are effective, they cause systemic toxicity
in the test animals at high doses.

Researcher Quijano-Rubio says that by controlling when and where drugs become active in the body, we may be able to make safer and more effective cancer therapies
.
In summary, the results of this study suggest that the immune cell targeting effect of these two drug components may be able to selectively expand the level of CD8+ T cells in a mouse model of synthetic melanoma, and promote the activation of chimeric antigen receptor T cells in a lymphonoma xenograft model, while enhancing the anti-tumor efficacy
of the body in both cases.
(Biovalley Bioon.
com)

Original source:

Quijano-Rubio, A.
, Bhuiyan, A.
M.
, Yang, H.
 et al.
 A split, conditionally active mimetic of IL-2 reduces the toxicity of systemic cytokine therapy.
 Nat Biotechnol (2022).
doi：10.
1038/s41587-022-01510-z