mRNA Vaccine to Prevent Colorectal Cancer Recurrence

The COVID-19 vaccines mark the first widespread use of mRNA technology. They work by using synthetic genetic code to instruct the patient’s cells to recognize the coronavirus and activate the immune system against the virus. But researchers began exploring how to use mRNA vaccines as a new way to treat cancer long before this technology was used against the coronavirus.

A B-cell displaying antibodies created in response to foreign protein fragments produced from a personalized mRNA vaccine recognizes a colorectal cancer cell and signals killer T-cells to destroy it

We’ve known about this technology for a long time, well before COVID-19,” says Van Morris, M.D. Here, he explains how mRNA vaccines work and how a team of MD Anderson colorectal cancer experts led by Scott Kopetz, M.D., Ph.D., are testing the technology in a Phase II clinical trial, following high-risk patients with stage II or stage III colorectal cancer who test positive for circulating tumor DNA after surgery.

The presence of circulating tumor DNA is checked with a blood test. “If there is ctDNA present, it can mean that a patient is at higher risk for the cancer coming back,” Morris says. The opposite can also be true: if there is not circulating tumor DNA present, the patient may have a lower risk of recurrence, he adds.

In the Phase II clinical trial, enrolled patients start chemotherapy after the tumor is surgically removed. Tissue from the tumor is sent off to a specialized lab, where it’s tested to look for genetic mutations that fuel the cancer’s growth. Morris explains anywhere from five to 20 mutations specific to that patient’s tumor can be identified during testing. The mutations are then prioritized by the most common to the least common, and an mRNA vaccine is created based on that ranking. “Each patient on the trial receives a personalized mRNA vaccine based on their individual mutation test results from their tumor.

As with the COVID-19 vaccines, the mRNA instructs the patient’s cells to produce protein fragments based off tumor’s genetic mutations identified during testing. The immune system then searches for other cells with the mutated proteins and clears out any remaining circulating tumor cells.We’re hopeful that with the personalized vaccine, we’re priming the immune system to go after the residual tumor cells, clear them out and cure the patient,” says Morris.

Source: https://www.mdanderson.org/

Powerful New Tool Against Cancer

All cells in the human body have a shelf-life, but those of the cancerous variety use some cunning trickery to outlive their expiry dates and continue spreading throughout the body. Scientists at the University of Tokyo have developed a synthetic version of a fungal compound that could help swing things back in our favor, by reactivating a missing gene that would normally drive these sinister cells to self-destruction.

As our cells fulfill their roles and edge towards the end of their lives, they undergo a form of programmed death called apoptosis, clearing the way for fresher and healthier cells. But with the help of genetic mutations, cancer cells are able to avoid this fate and go on multiplying to form tumors.

Targeting this mechanism and initiating apoptosis in cancer cells has been a major focus for researchers in the field, with compounds in olive oil and others that flush them with salt a couple of techniques that have shown promise in recent times. And in a naturally occurring compound found in the fungus species Ascochyta, scientists uncovered another exciting possibility.

Previous experiments had shown this compound, called FE399, could trigger apoptosis in cancer cells in vitro, by reinstating the self-destruct gene that drives the programmed death process. The compound had shown particular promise against colorectal cancer, but the complex nature of the compound meant that reproducing it in meaningful quantities was a tall order. Extracting natural versions of FE399 from the fungus was not a viable option, setting up a significant roadblock for use of this promising anti-cancer compound. But the University of Tokyo team was determined to find a way forward, and set out to develop a complete, synthetic version of the compound to pave the way for mass production.

CLICK ON THE IMAGE TO ENJOY THE VIDEO

We wanted to create a lead compound that could treat colon cancer, and we aimed to do this through the total synthesis of FE399,” says Professor Isamu Shiina, study author.

The team started by identifying the complex structure of the compound. A long process of trial and error followed until, in what the researchers describe as a major breakthrough, they produced a trio of spots on a plate bearing exactly the same chemical signature as FE399.

We hope that this newly produced compound can provide an unprecedented treatment option for patients with colorectal cancer, and thus improve the overall outcomes of the disease and ultimately improve their quality of life,” says Professor Shiina.

The research was published in the journal European Journal of Organic Chemistry.

Source: https://newatlas.com/

How To Reverse Cellular Aging Process

Central to a lot of scientific research into aging are tiny caps on the ends of our chromosomes called telomeres. These protective sequences of DNA grow a little shorter each time a cell divides, but by intervening in this process, researchers hope to one day regulate the process of aging and the ill health effects it can bring. A Harvard team is now offering an exciting pathway forward, discovering a set of small molecules capable of restoring telomere length in mice. Telomeres can be thought of like the plastic tips on the end of our shoelaces, preventing the fraying of the DNA code of the genome and playing an important part in a healthy aging process. But each time a cell divides, they grow a little shorter. This sequence repeats over and over until the cell can no longer divide and dies.

This process is linked to aging and disease, including a rare genetic disease called dyskeratosis congenita (DC). This is caused by the premature aging of cells and is where the team focused its attention, hoping to offer alternatives to the current treatment that involves high-risk bone marrow transplants and which offers limited benefits.

One of the ways dyskeratosis congenita comes about is through genetic mutations that disrupt an enzyme called telomerase, which is key to maintaining the structural integrity of the telomere caps. For this reason, researchers have been working to target telomerase for decades, in hopes of finding ways to slow or even reverse the effects of aging and diseases like dyskeratosis congenita.

Once human telomerase was identified, there were lots of biotech startups, lots of investment,” says Boston Children’s Hospital’s Suneet Agarwal, senior investigator on the new study. “But it didn’t pan out. There are no drugs on the market, and companies have come and gone.

Source: https://news.harvard.edu/
AND
https://newatlas.com/

Aggressive cancers in ‘evolutionary arms race’ with the immune system

Aggressive and highly-mutated cancers are engaged in an “evolutionary arms race” with the immune system, new research suggests. Gullet and stomach cancers with faults in their systems for repairing DNA build up huge numbers of genetic mutations which make them resistant to treatments like chemotherapy. But these numerous mutations mean they appear foreign to the immune system, leaving them vulnerable to attack, and susceptible to new immunotherapies.

Scientists at the Institute of Cancer Research, London (ICR), found that these “hyper-mutant” tumours rapidly evolve strategies to disguise themselves from the immune system and evade attack. They hope that in the future, the findings could help optimise treatment with immunotherapy, and other drugs such as chemotherapy.

Dr Marco Gerlinger, team Leader in translational oncogenomics at the ICR, said: “Our new study has shown that in highly mutated tumours, cancer and the immune system are engaged in an evolutionary arms race in which they continually find new ways to outflank one another.

Watching hyper-mutated tumours and immune cells co-evolve in such detail has shown that the immune system can keep up with changes in cancer, where current cancer therapies can become resistant – and that we could use immunotherapies to shift the balance of this arms race, extending patients’ lives.

“Next, we plan to study the evolutionary link between hyper-mutant tumours and the immune system as part of a new clinical trial looking at the possible benefit of immunotherapy in bowel cancer.

The study has been published in Nature Communications.

Source: https://www.sciencefocus.com/

Cancer’s ‘Internal Wiring’ Predicts Relapse Risk

The “internal wiring” of breast cancer can predict which women are more likely to survive or relapse, say researchers. The study shows that breast cancer is 11 separate diseases that each has a different risk of coming back. The hope is that the findings, in the journal Nature, could identify people needing closer monitoring and reassure others at low risk of recurrence.

Cancer Research UK said that the work was “incredibly encouraging” but was not yet ready for widespread use. The scientists, at the University of Cambridge and Stanford University, looked in incredible detail at nearly 2,000 women’s breast cancers. They went far beyond considering all breast cancers as a single disease and beyond modern medicine’s way of classifying the tumours.

Doctors currently classify breast cancers based on whether they respond to the hormone oestrogen or targeted therapies like Herceptin. The research team analysed the genetic mutations inside the tumour to create a new way of classifying them.

By following women for 20 years, they are now able to show which types of breast cancer are more likely to come back.  “This is really biology-driven, it’s the molecular wiring of your tumour, said Prof Carlos Caldas. Once and for all we need to stop talking about breast cancer as one disease, it’s a constellation of 11 diseases. “This is a very significant step to more precision-type medicine.”

Source: https://www.bbc.com/