Reporter of Science and Technology Daily Liu XiaSalmonella usually causes food poisoning, but in 2019, 71 year old Canadian Irit Barbour volunteered to drink a bottle of liquid containing 1 billion active Salmonella typhimurium as the last resort to fight pancreatic cancer. At that time, pancreatic cancer had spread to other organs in her body, and she could only live for a few months

Reporter of Science and Technology Daily Liu Xia

Salmonella usually causes food poisoning, but in 2019, 71 year old Canadian Irit Barbour volunteered to drink a bottle of liquid containing 1 billion active Salmonella typhimurium as the last resort to fight pancreatic cancer. At that time, pancreatic cancer had spread to other organs in her body, and she could only live for a few months. The Salmonella she drank has been genetically modified to attack cancer cells and has less toxicity to other parts of the body than ordinary Salmonella. Barber was the first person in the world to try Salmonella therapy while undergoing chemotherapy, and the results showed that her tumor had shrunk to 10% of its original size.

Recently reported on the website of New Scientist magazine in the UKNew research suggests that some bacteria and fungi that inhabit tumors can affect the progression and treatment of cancer, potentially becoming a new weapon in the arsenal against cancer.Some related drugs are currently undergoing clinical trials, and these microorganisms can penetrate into areas that are difficult to reach with existing therapies such as chemotherapy, providing alternative methods for attacking tumors.

Image source: New Scientist website

Tumors are a "safe haven" for bacteria

Bacteria, fungi, viruses and other microorganisms inhabit people's intestines and affect human health in a variety of ways. In 2020, Irana Leviathan and her colleagues from the Weizmann Institute of Science in Israel reported in the journal Science that after analyzing over 1000 human tumor samples, they found that the tumors were also filled with microorganisms.

Through gene sequencing, Leviathan identified bacteria in eight types of tumors in humans, including the breast, brain, lungs, skin, bones, ovaries, pancreas, and colon. Colon and breast tumors typically carry more bacteria, and they even found unique bacterial populations in each type of cancer.

In the same year, the Leviathan team released explosive news: they also discovered fungi in the 8 types of tumors they had previously studied. The team led by Ilian Iliev of Cornell University in New York, USA, also published a paper in the journal Cell, saying that after studying gastrointestinal tumors, lung cancer and breast cancer, they found that these tumors often contain candida, blastomyces, Malassezia and other fungi.

Utilizing microorganisms to combat tumors

There are various reasons why microorganisms are attracted to tumors, but scientists are increasingly aware that their presence can affect the progression and treatment of cancer.

For example, Ilyev et al. found that higher levels of Candida in gastrointestinal tumor cells are associated with higher pro-inflammatory gene activity, cancer metastasis rate, and lower cancer survival rate. In addition, Fusobacterium tuberculosis can promote the occurrence of cancer, accompany its spread to other parts of the body, and inhibit its response to chemotherapy.

For decades, scientists have known that human papillomavirus (HPV), hepatitis B virus (HBV) and other viruses can trigger the formation of cancer, and HPV and HBV vaccines have also been developed to help prevent the occurrence of related cancers. Robert Holt from the Cancer Research Institute in British Columbia, Canada, said that people may be able to "follow the example" and develop vaccines against oncogenic bacteria, using them to slow down tumor progression, strengthen the response to chemotherapy, and even prevent tumor formation from the beginning.

The Holt team is specifically developing a vaccine against Fusobacterium nucleatum. The vaccine contains Messenger RNA (mRNA), which can guide the body to manufacture certain protein fragments found in this bacterium, and train the immune System identification to recognize and kill this microorganism. The vaccine is still being tested on mice, and Holt et al. hope to one day conduct trials on patients with Fusobacterium nucleatum positive colon cancer who have failed conventional therapy.

Removing "harmful" microorganisms from tumors is one strategy for attacking cancer, while introducing "beneficial" microorganisms is another strategy. Gerard Baptiste, an oncologist in charge of the treatment of Barbour in Montreal Jewish General Hospital, Canada, said that the genetically modified Salmonella would directly enter the tumor and carry Interleukin 2, which can activate the immune system, to produce anti-tumor immune activity at the tumor site.

Based on the therapeutic effect of Barbour, the Battista team launched a phase II clinical trial in 2020. Twenty patients with stage 4 metastatic pancreatic cancer received standard chemotherapy and the treatment of genetically modified salmonella. The results released in January this year showed that the average lifespan of participants was 24 months, while the typical survival period for patients who only received standard chemotherapy was 11 months, and Salmonella did not make these volunteers sick.

Emerging anticancer therapies have broad prospects

Baptiste pointed out that one of the main advantages of this method is that the manufacturing cost of bacteria is far lower than other Cancer immunotherapy. The Food and Drug Administration (FDA) recently gave Salmonella a fast track therapy. If it passes future trials, it will be marketed as soon as possible.

A Swiss company called "T3 Pharmaceuticals" is also using bacteria to strengthen the immune system in response to cancer. Christopher Casper, the chief scientific officer of the company, said that they were testing a bacterium called Yersinia enterocolitica, which is a pork pollutant that can lead to food poisoning, but genetic modification can "reduce its toxicity". The uniqueness of this type of bacteria lies in the special "nanoinjector" on its surface, which is used by bacteria to inject proteins into cells. T3 Pharmaceutical Company has designed a Yersinia enterocolitica that can inject protein into tumor cells to release Signaling molecule, so that the immune system can play a role in fighting against tumors.

When the genetically programmed Yersinia enterocolitica was injected into the blood of mice with Melanoma, they selectively attached to the tumor, resulting in up to 2/3 of the tumor disappearance, and no serious side effects were observed. The company has just launched a human clinical trial of genetically programmed Yersinia enterocolitica for the treatment of solid tumor patients.

BioMed Valley Discoveries, headquartered in Missouri, USA, is studying the ability of Clostridium to attack tumors. They use it in combination with checkpoint inhibitor Pembrolizumab. Brent Clyde, president of the company, said that the test principle is to let bacteria fight against tumors from the inside out, and let Pembrolizumab fight against tumors from the outside in order to achieve internal and external pinch. The results will be announced later this year.

Editor: Wang Yu

Reviewed by: Zhang Shuang

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