A vaccine to prevent colorectal cancer

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Medical personnel worldwide are developing new human antigen vaccines, including various types of cancer preventive and therapeutic. Click for details: The light of hope to end cancer-2019 global inventory of the latest cancer vaccine! (Covering six major cancers).

Immune cells (pink and red) attack tumor cells (blue) that produce new antigens (blue and orange). Vaccines can help train immune cells to recognize new antigens.

Recently, scientists have developed a vaccine that can destroy the mutant cells made by Lynch syndrome (Lynch) DNA in mice, and may one day prevent people with the genetic disease Lynch syndrome from developing colorectal cancer.
The study reported that in a Lynch syndrome (Lynch) mouse model, vaccination with as few as four tumor antigens can produce an antigen-specific response, reduce intestinal tumors, and improve survival.
According to the data provided by the recent AACR annual meeting, this pre-human study shows that it is possible to develop a vaccine to prevent cancer in patients with Lynch syndrome.

Carcinogenic genetic disease-Lynch syndrome

Lynch syndrome, commonly referred to as hereditary nonpolyposis colorectal cancer (HNPCC), is an inherited disease that may be caused by mutations in genes inherited from parents to children and increases the risk of many types of cancer , Including colon cancer, endometrial cancer, ovarian cancer, gastric cancer, small intestine cancer, pancreatic cancer, kidney cancer, brain cancer and cholangiocarcinoma. Especially colon cancer and rectal cancer. People with Lynch syndrome have a 70% to 80% risk of colorectal cancer.
In the United States, approximately 140,000 new cases of colorectal cancer are diagnosed each year. About 3% to 5% of these cancers are caused by Lynch syndrome.

A vaccine to prevent Lynch syndrome

At present, patients with Lynch syndrome can only avoid colorectal cancer through frequent screening and prevention. Low-dose aspirin has also been shown in clinical trials to reduce the risk of colorectal cancer.
And vaccines can provide another, potentially more effective way to stop the development of cancer.
Recently, researchers have taken an important step in the development of vaccines to prevent the high-risk disease of cancer, Lynch syndrome (Lynch).
Scientists led by Steven Cornkin, MD, of Weill Cornell, reported the results of NCI-funded cancer prevention vaccine tests at the recent annual meeting of the American Association for Cancer Research. Compared with unvaccinated mice, this vaccine prevented the growth of colorectal tumors and extended the survival of mice in the Lynch syndrome mouse model.
The principal investigator, Dr. Lipkin, and vice-chairman of research at the Department of Medicine in New York, plans to identify common neoantigens that occur in early colorectal tumors in patients with Lynch syndrome. The project was funded by the National Cancer Institute (NCI) through the Cancer “Moon Exploration Program” immuno-oncology transformation network.
Dr. Lipkin pointed out that if human trials of cancer prevention vaccines do make progress, it will take several years to determine whether it is effective.
At the same time, his team is using mouse models to better understand how the vaccine works and how the growing cancer cells resist its effects.

Discovery of common mutations in Lynch syndrome cancer

Lynch syndrome is caused by inherited genetic mutations, which can prevent the repair of DNA errors that occur during cell division. Such errors are called mismatch repair defects.
This is like not using a DNA spell checker. Without this defense, DNA errors will accumulate in the cells and may eventually lead to various cancers.
Short repeating DNA fragments called microsatellites are particularly prone to DNA mismatches. Tumors with mismatch repairs will eventually accumulate changes in these microsatellites. This situation is called microsatellite instability.
Microsatellite unstable tumors may produce new proteins, called new antigens, which are foreign  substances to the body and can trigger the immune system to attack the cells that make these proteins.
As a result, the researchers found more important information. Tumors formed in people with Lynch syndrome often have the same microsatellite mutations, such as in 60% to 80% of people with colorectal cancer that has a mismatch repair defect. There will be specific microsatellite mutations in the TGFBR2 gene.

Development and optimization of cancer vaccines

In 2011, researchers from the National Cancer Research Center in Heidelberg, Germany, began clinical trials of new antigen vaccines in people with advanced colorectal cancer. These patients have high microsatellite instability.
First, the scientists searched DNA from 32 colorectal tumors found in the Lynch syndrome mouse model and identified 13 common mutations.
The researchers then used an algorithm to predict which shared mutations would produce new antigens, and finally identified 10 species. When they injected these 10 new antigens into mice, four of them triggered a strong immune response.
These four new antigens are combined to produce a mouse vaccine. They found that the use of vaccines and adjuvants in a mouse model of Lynch syndrome can reduce the development of colorectal tumors and prolong survival.
“This is one of the first cancer immunopreventive vaccines using new antigens that may be formed by DNA mismatch repair defects,” Dr. Umar said.
Next, the researchers determined whether combining the vaccine with other treatments could improve its efficacy. For example, Naprosyn, a commonly used analgesic, has been shown to be superior to aspirin or control in reducing the development of colorectal tumors in mouse models. Naproxen also seems to enhance the efficacy of the vaccine. Mice treated with vaccine plus naproxen lived longer than mice vaccinated alone or vaccinated plus aspirin. Immune cells in the vaccine plus naproxen group were better able to recognize the new vaccine antigen than mice in the vaccine alone or vaccine plus aspirin group.

Conclusion

People with Lynch syndrome will be candidates for cancer prevention vaccines,If developed.
Current NCCN guidelines recommend microsatellite instability testing for people with colorectal cancer and endometrial cancer. If the patient’s tumor test is positive for microsatellite instability, it is recommended that it be tested for Lynch syndrome. If it is diagnosed as Lynch syndrome, it is recommended to test the first-degree relatives of the patient to prevent it from happening.
It is recommended that high-risk groups can be screened for genetic susceptibility genes for tumors. For specific types of screening, please consult the Global Oncologist Network Medical Department (400-666-7998), and select based on personal family history and risk factors:

  • Cancer genetic susceptibility gene detection (a total of 139 genes):
  • Covers 139 genes in the human genome that are genetically related to cancer, involving 20 types of cancer and 70 types of cancer-related genetic syndromes
  • Tumor genetic susceptibility gene test (23 common genes):
  • Involves 8 kinds of high-risk cancer and 14 kinds of common genetic syndromes
  • Cancer genetic susceptibility gene test (18 genes for women):
  • Involves 3 types of high-risk female tumors and 5 types of related genetic syndromes
  • Cancer genetic susceptibility gene detection (17 genes in digestive tract):
  • Involves 5 types of high-risk digestive tract tumors and 8 types of related genetic syndromes
  • Breast cancer + breast cancer: BRCA1 / 2 gene
  • Colorectal cancer: 17 genes
  • All tumors: 44 genes

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