Sub-Journal of "Science": New-concept drug shields can solve the side effects of anticancer drugs

When it comes to chemotherapy, many people are worried about the side effects of drugs, because when chemotherapy drugs kill tumors, they also accidentally damage normal cells and tissues
.

As the current hot spot, immunotherapy is also difficult to avoid this effect
.

Such drugs are usually antibodies or cytokines that have been modified in vitro.

Since these drugs are injected intravenously, they will spread throughout the body with the blood, not just confined to the tumor area
.

Therefore, normal tissues are difficult to avoid being affected by drugs

The effectiveness of many immunotherapy drugs or immunomodulators has been supported by some studies, but if the toxicity of the drugs cannot be reduced, it will be difficult to achieve popularization and application
.

Is there a way to be safe and effective at the same time? The study published by Tang's team in Science Advances shows a new method that allows immunotherapy molecules to be activated only when they encounter a tumor
.

The first thing the research team considered was the special chemical properties surrounding the tumor
.

Because the tumor microenvironment is significantly different from other areas of the body, especially the pH around the tumor is very low, which means that this area is more acidic and has a higher reduction potential

This special environment has become an exploitable weakness, or a condition for drug activation
.

The researchers designed a stimulus reaction chemical bond for this purpose, which will be connected to the drug and specifically respond to the chemical conditions of the tumor microenvironment

▲The chemical bond will only break in the tumor environment, thereby releasing the drug in the protective cover (picture source: reference [1])

In normal cell tissues, chemical bonds will not be destroyed, so the drug will not be released
.

When the drug moves to a tumor with a very low pH value, the chemical bond will react and cause it to break.

So what is the actual effect of this method? The researchers selected a group of mice with colon adenocarcinoma, a model mouse that has been verified to respond to antibody therapy
.

Subsequently, they used a new method to encapsulate an antibody anti-4-1BB, which has been proved to be a candidate for anti-cancer therapy, but its toxicity is too strong to limit its use

After intraperitoneal injection, the researchers observed that even if the anti-4-1BB is wrapped, it can still obtain the anti-tumor effect of direct injection of antibodies, which indicates that the drug in the protective cover will be released
.

In addition, the immune response it causes is more precise.

▲The new method has very low cytotoxicity, and direct use of antibodies will cause liver and pancreas damage (red box) (picture source: reference [1])

In addition to colon adenocarcinoma, the new technology can also be used to treat mice with melanoma
.

In this model mouse, the researchers used interferon-15 (IL-15) as the test drug

The researchers said that this method allows the drug to specifically attack the tumor without damaging normal tissues
.

Note: The original text has been deleted

Reference source:

[1] Yu Zhao et al.
, (2021), Switchable immune modulator for tumor-specific activation of anticancer immunity.
Science, DOI: 10.
1126/sciadv.
abg7291

[2] New immunotherapy method targets tumor tissue only.
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