Cancer tumors are particularly adept at evading the body’s immune response, making them difficult to treat. A new study genetically engineered common gut bacteria so that they can seek out and destroy cancerous tumors from the inside out.
There are multiple ways tumors survive by evading the body’s immune response. One is to prevent immune cells from engaging in chemotaxis, the process by which immune cells detect tumors, migrate toward them, and begin attacking them. Chemotaxis is driven by cytokines, small proteins that signal other immune cells. Chemokines are a subset of cytokines that cause immune cell migration.
The chemokine CXCL16 recruits T cells, white blood cells that help fight infection and cancer, to infiltrate cells. CXCL16 and its receptor CXCR6 have been shown to improve survival in colon and lung cancer patients. Also, recent studies suggest that CXCL16 and CXCR6 together generate anti-tumor immunity. However, no one has found a way to deliver CXCL16 into the tumor’s cellular milieu.
Scientists have long known that certain bacteria can survive inside tumors. created a method to target and destroy tumors by mobilizing
“Decades of research have allowed us to understand how the immune response develops. [we’re] Senior author of the study, Dr. Nicholas Arpais, said:
Critical to this study was the introduction of an engineered probiotic strain Escherichia coli (Escherichia coli), a bacterium common to the human gut.of Escherichia coli It was designed to contain a synchronous lytic cycle, a method that takes advantage of the innate ability of some bacteria to invade disease sites in the body.
When bacteria enter a tumor, a circuit kicks in and causes the bacteria to break down or dissolve. Lysis enables repeated local delivery of chemokines that recruit T cells and enhance anti-tumor immunity.
In 2019, the same researchers engineered a strain of non-pathogenic bacteria that behaves like a Trojan horse that invades mouse tumors and attacks them from within. They found that genetically engineered bacteria eliminated tumors and reduced the incidence of tumor metastasis.
In the current study, in addition to using engineered bacteria, researchers combined the expression of CXCL16 with another chemokine, CCL20. CCL20 attracts lymphocytes, a type of white blood cell, and dendritic cells, powerful cells responsible for initiating adaptive immune responses by presenting antigens to other immune cells.
Researchers have found that combining two chemokines enhances therapeutic efficacy and enhances the immune response against tumors in a way not previously available.
“Combining this with chemokines that promote the infiltration and activation of dendritic cells, an important innate immune cell type, improves the detection of tumor antigens,” said Arpaia.
Their experiments in mice showed that the engineered bacteria produced potent immune responses against tumors directly injected with the bacteria and against more distant tumors that were not injected. , the bacteria did not affect healthy tissue.
“What we are seeing is that bacteria only colonize the tumor environment and only reach a sufficient level of quorum within the tumor to induce lysis, thus allowing the bacteria to spread in other healthy organs. This means that it cannot be detected.
Researchers continue to perfect the technology with a view to using it in human clinical trials.
The study was published in a journal scientific progress.
Source: Columbia University
