Research results demonstrate the potential of bacterial vaccines as a treatment for cancer immunotherapy

New York: Columbia researchers develop probiotic bacteria that train the immune system to eliminate cancer cells, paving the way for a new type of cancer vaccination that harnesses bacteria’s innate tumor-targeting ability. Ta. These microbial cancer vaccines can be tailored to each person’s specific original tumor and metastases, potentially preventing future recurrences.
In mouse models of advanced colorectal cancer and melanoma, bacterial vaccines stimulate the immune system and primary and metastatic malignancies shrink or, in many cases, disappear completely. Leave healthy body parts alone.
The results of this study were published in the journal Nature.
Bacterial vaccines have proven to be particularly effective than peptide-based therapeutic cancer vaccines that have been used in numerous cancer clinical trials to date.
“A key advantage of our system is its unique ability to coordinately reconstitute and activate all arms of the immune system to induce a productive anti-tumor immune response. This is why this system is particularly challenging. “We believe that’s why it works so well in advanced solid tumor models that require treatment with other immunotherapies,” said study leader Dr. Vagelos, an internist at Columbia University. said Andrew Redenti, MD/PhD student in the College of Surgeons.
“The net effect is that the bacterial vaccine can control or eliminate the growth of aggressive primary or metastatic tumors and extend survival in mouse models,” said the author, who led the bacterial engineering aspect of the study. says Jeongwon Im, a doctoral student at Columbia University. .
Bacterial vaccines are individualized for each tumor. “Every cancer is unique. Tumor cells have distinct genetic mutations that distinguish them from normal, healthy cells. Programming bacteria to direct the immune system to these cancer-specific mutations “This allows us to develop more effective treatments by stimulating the patient’s own immune system to detect and kill cancer cells,” said Tal, associate professor of biomedical engineering at Columbia University’s School of Engineering.・Dr. Nicholas Arpaia, associate professor of microbiology and immunology at Columbia University Vagelos College of Physicians and Surgeons, who led the study with Dr. Danino, said: .
“As we continue to integrate additional safety optimizations through further genetic programming, we are getting closer to testing this therapy in patients,” he added.
Bacteria have been used to treat cancer since the late 19th century, when Dr. William Coley, a surgeon at a New York hospital, observed tumor regression in some patients with inoperable tumors who were injected with the bacteria. The bacterium is still used as a treatment for patients with early-stage bladder cancer. Researchers now know that some bacteria can naturally migrate to and colonize tumors, multiply in environments that are often depleted of oxygen, and trigger local immune responses. Masu.
But when used in this way, bacteria usually cannot precisely control or direct the immune response that attacks cancer. “Although these properties alone usually do not give bacteria enough power to stimulate a tumor-destroying immune response, they are a good starting point for building a new area of ​​cancer treatment.” said Dr. Nicholas Arpaia.
The new system starts with a probiotic strain of E. coli. The researchers then made multiple genetic modifications to control precisely how the bacteria interact with the immune system and educate the immune system to induce tumor killing.
The genetically engineered bacteria encode protein targets called neoantigens that are specific to the cancer being treated. Delivered by bacteria, these neoantigens train the immune system to target and attack cancer cells that express the same proteins. As neoantigens are used as tumor targets, normal cells lacking these cancer-marking proteins are left alone. Due to the nature of the bacterial system and additional genetic modifications engineered by scientists, these bacterial cancer treatments also overcome the immunosuppressive mechanisms that tumors use to block the immune system.
These genetic modifications are also designed to block the bacteria’s natural ability to evade immune attacks against itself. As a safety measure, this means that the genetically engineered bacteria are easily recognized and eliminated by the immune system, and if no tumor is found, they are quickly removed from the body.
When tested in mice, the researchers found that these intricately programmed bacterial cancer vaccines mobilized a wide range of immune cells to attack tumor cells, while launching an immune attack normally directed at tumors. They discovered that it blocks the suppressive response.
The bacterial vaccine also inhibited cancer growth when administered to mice before tumors developed, and also prevented the same tumors from regrowing in cured mice, suggesting that the vaccine may be used in patients who have had cancer. It was suggested that this drug may have the ability to prevent the recurrence of cancer. Remission.
For humans, the first step in creating these microbial vaccines is to use bioinformatics to sequence a patient’s cancer and identify its unique neoantigens. Bacteria would then be engineered to produce large amounts of the identified neoantigens and other immunomodulatory factors. When injected into a patient whose tumor is being treated, the bacteria travel to the tumor, take up residence, and steadily produce and deliver large quantities of man-made “medicines.”
Bacterial vaccines activate the immune system, prompting it to eliminate cancer cells that have spread throughout the body and prevent further spread.
Because each tumor has its own set of neoantigens, immunotherapy is customized for each patient. “The time to treatment depends on how long it takes to sequence the tumor first. Then we just need to create the bacterial strain, which could be done very quickly. “Bacteria is easier to manufacture than some other vaccine platforms,” ​​Danino said.
The bacterium is also designed to counter cancer’s ability to rapidly mutate and evade treatment. “With our platform, we can deliver so many different neoantigens that, in theory, tumor cells would lose all of these targets at once, making it difficult for them to evade the immune response.” Arpaia says.
The researchers believe their approach could succeed where earlier cancer vaccines failed. In the latter, an immune response against tumor neoantigens may be induced, but direct modulation of the immunosuppressive tumor environment is not achieved to such extent.
Dr. Arpaia further added, “Bacteria enable the delivery of higher concentrations of drugs than would be tolerated if these compounds were delivered systemically throughout the body. Here, we limit delivery directly to the tumor and “We can locally adjust how we stimulate the immune system.” ”

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