Nontoxic drug delivery system could lead to effective therapies for currently untreatable cancers


Figure 1: The intracellular lifestyle of Salmonella is regulated by flhDC. The design goals are (1) a bacterium that synthesizes a protein drug (yellow / purple), (2) actively invades cancer cells, and (3) releases a drug that escapes from Salmonella vacuoles (SCV, red). It was to genetically engineer the vehicle. .. Intracellular report of 2 × 106 CFU in subcutaneous 4T1 tumors of b, c BALB / c mice 96 hours after intratumoral injection of Salmonella, intracellular (green; black arrow) rather than extracellular (white arrow; P) There were many bacteria (red).

A non-toxic, bacteria-based system developed at the University of Massachusetts at Amherst can detect that it is inside cancer cells and release the therapeutic drug payload directly into the cells.Works published in Nature Communications Today, it can lead to effective targeted therapies for cancers that are currently incurable, such as liver cancer and metastatic breast cancer.

The inability to penetrate solid tumor cell membranes has traditionally prevented researchers from effectively targeting important cancer pathways. Current delivery methods, such as nanoparticles, cell-permeable peptides, and antibody-drug conjugates, have limited effectiveness due to their low ability to penetrate. cell, Can’t be specifically targeted cancer cell, And their susceptibility to degradation by nature maintenance of cells to foreign invaders.

Breakthrough UMass Amherst research has demonstrated in the laboratory that not only can cells easily invade, but cancer cells can be specifically targeted to deliver proteins (drugs) directly, leaving healthy cells intact. .. And when the protein payload is delivered, the bacteria dissipate and become transparent.

“We can actually detect [the protein] It cannot be detected in the liver or spleen of a mouse model, “said Neil Forbes, a researcher at the Institute of Chemical Engineering and Applied Life Sciences.When we saw Immune response And that Liver hurts, No difference from saline was seen. “

The delivery system was developed by Nele Van Dessel, a bioengineer and co-lead author of the paper, as a postdoc in Forbes’ lab. It uses a highly modified type of Salmonella that is injected into the bloodstream.

Salmonella is known to accumulate in tumors, but was not known to invade cancer cells. Van Dessel’s system can accurately measure this cell permeability as the manipulated Salmonella turns green when it breaks through the cell membrane.

“Salmonella in cancer cells—no one has ever actually shown this,” says Forbes.

The proteins used were developed by Jeanne Hardy in Chemistry, Molecular Biology and Cell Biology, and the research was led by Van Dessel and Vishnu Raman, co-lead authors of the paper in Chemical Engineering.

Although still preclinical, test results in mice are very promising, especially hepatocellular carcinoma, which is the most common type of liver cancer diagnosed by 840,000 people worldwide each year. Currently, few drugs are available to treat liver cancer.

“For liver cancer,Clinical evidence Forbes said in his lab study that “it has an antitumor effect. This is early in just a few mice, but it uses this treatment to repel these tumors. “.

Developing effective treatments for untreatable cancers will be particularly satisfying, as it does not currently exist, says Vandessel.Two of her Family members “I felt helpless,” she says, when she was diagnosed with stage 4 solid cancer in 2016. “I got a PhD in cancer research and worked for 10 years but couldn’t help them. I felt like they had failed and didn’t work hard enough. “

This prompted Vandessel, along with Forbes, to launch Ernest Pharmaceuticals with the goal of bringing bacterial cancer technology to the clinic. The company is named after Forb’s grandfather, who died of prostate cancer.

The university has applied for a patent on this study and has licensed it to Ernest Pharmaceuticals. Both company executives Van Dessel and Raman seek FDA approval for clinical trials.

“We hope we’ll be in the clinic in a couple of years,” says Van Dessel, and it’s liver And chest cancer“Ernest also focuses on the ovaries and pancreas. Many of the current immunotherapies and other therapies do not have a significant impact on these tumors.”

New artificial intelligence brings hope to patients with liver cancer who have less than 13% chance of survival

For more information:
Vishnu Raman et al, Intracellular delivery of protein drugs using an autonomously lysing bacterial system reduces tumor growth and metastasis, Nature Communications (2021). DOI: 10.1038 / s41467-021-26367-9

Quote: Non-toxic drug delivery system, currently incurable cancer obtained on October 21, 2021 from https: // May lead to effective treatment (October 21, 2021)

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