May 22, 2022


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This is why many cancer trials are so hard to repeat

This is why many cancer trials are so hard to repeat

Cancer biologist Cyrus Gypsy was preparing to seek an immunotherapy for breast cancer when he encountered an obstacle: fast-spreading cancer cells he transplanted into mice stayed in place and sometimes even disappeared after 11 days. Candice Grzelak, who was involved in the research, identified the culprit: green fluorescent protein (GFP)that scientists used to track cells. The marker was found to stimulate the rodents’ immune system to attack cancer cells.

This phenomenon reflects this A broader problem in immunotherapy researchAnti-cancer treatments that stimulate the body’s immune system to fight the intruder. Proteins that biologists use to target cancer cells, such as GFP is derived from the jellyfish Aequorea victoria, can provoke an attack on these modified tissues. A similar effect may occur with other foreign proteins used in laboratory tests (eg components of the CRISPR/Cas9 system).

“This phenomenon may explain why laboratories are sometimes unable to replicate immunotherapy results for other groups,” said Glenn Merlino, a cancer biologist at the National Cancer Institute (NCI).

Contrary to appearances, Such a procedure of GFP is not helpfulAnd problematic because it interferes with the course of the experience itself.

Thus, many preclinical trials do not lead to anything useful. Glenn Merlino, co-author of the study, added that the research is not in some way about getting rid of cancer, but about learning how to do it every time it occurs.

Although scientists realize that the immune system can sense marker proteins (such as GFP), this has not been of great importance in cancer research until now. it’s because of Most labs use genetically modified micedeprived of the immune system, so as not to reject the transplanted human cells.

Due to the success of immunotherapy in recent years, more and more teams are working More than mice with a healthy immune system.

NCI scientists warn that a similar problematic immune response could emerge in experiments using other fluorescent proteins of different types, cancer-causing viral proteins, and even Cas9, the enzyme that cuts CRISPR DNA that comes from bacteria. will be necessary Alternative solution to this problemfor example, modified strains of mice to tolerate foreign proteins.

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