'New paradigm' moment as mRNA cancer vaccine developed

‘New paradigm’ moment as mRNA cancer vaccine developed by Covid shot maker Moderna slashes risk of tumor relapse or death in melanoma patients by 44%

  • The cancer vaccine will be personalized according to each patient’s tumor cells
  • It works by teaching the immune system to recognize and attack cancer cells
  • Data from the latest vaccine trial showed it was 44 percent more effective

An experimental cancer vaccine using the same technology as in Covid shots slashed the risk of tumor relapse or death by 44 percent in clinical trials.

Pharma giants Merck and Moderna which developed the shot heralded the results as a ‘tremendous step forward’ and a ‘new paradigm moment’.

The new shot was compared to those who only received the immunotherapy Keytruda in stage two clinical trials involving 150 high-risk melanoma patients.

Doctors will now ‘rapidly’ seek approval for a final stage clinical trial, before getting approval to offer the vaccine to patients.

Revealing their work back in October, the scientists said the new vaccine could be ready in months. 

The new shot — designed for people with high-risk melanoma — is in the second of three trials and a verdict on whether it works or not is expected within months. It harnesses mRNA technology that delivers pieces of genetic code from patients’ tumors into their cells and teaches the body to fight off the cancer. The vaccine is given to people post-surgery to prevent the tumor from returning, and it is tailored to each patient, meaning no two shots will be the same

The new shot — designed for people with high-risk melanoma — harnesses mRNA technology that uses pieces of genetic code from patients’ tumors to teach the body to fight off cancer cells.

It is given to people post-surgery to prevent the tumor from returning and is tailored specifically to each patient, meaning no two shots are the same.

This means it could be hugely expensive. Similar cancer vaccines being trialed cost around $100,000 (£91,000) to make each individual shot

For over a decade, cancer researchers have been working on individualized cancer vaccines, using technology including mRNA.

Messenger RNA, or mRNA, is genetic material which tells the body how to make proteins.

The mRNA Covid vaccine teaches cells in the body how to make a protein which sets off an immune response.

The immune response generates antibodies, so that if the body is exposed to the real virus later, the body will recognize it and know how to fight it off.

With a cancer vaccine, researchers aim to bring out an immune response to fight abnormal proteins, known as neoantigens, made by cancer cells.

The manufacturing process for the vaccine begins by identifying the genetic mutations in a patient’s tumor cells that could release neoantigens.

The patient will have had the tumor surgically removed, meaning scientists can easily look at the tumor’s cells.

Computer algorithms judge which neoantigens are most likely to latch onto receptors on white bloods cells and trigger an immune response.

The personalized jab can hold genetic sequences for up to 34 different neoantigens.

It is hoped that the mRNA vaccine will then activate white blood cells which can recognize individual cancer cells thanks to the cancer cells’ neoantigens.

The vaccine will effectively teaches the immune system that cancer cells are different to the rest of the body.

This will hopefully not be too hard, as neoantigens do not form on normal cells.

Once tissue samples have been gathered from a patient, it takes between one and two months to make a personalized mRNA cancer vaccine.

A previous Moderna-sponsored study of a personalized cancer vaccine on patients with head and neck cancer saw the biotech company produce each individualized shot in around six weeks.

Because of the specialized nature of the vaccines, each one can cost up to $100,000.

Source: National Cancer Institute, CDC 

In the latest phase 2 study, 157 patients were given the personalized vaccines alongside Merck’s immunotherapy drug Keytruda.

All had stage three or four melanoma, the most dangerous types, and were given the treatment after tumors were surgically removed.

They were compared to a control group who also had high-risk melanoma, but only received the immunotherapy Keytruda.

The combination showed a statistically significant benefit compared to Keytruda alone after a year of treatment.

MRNA is leading the frontier of potential cancer cures after the technology was rapidly accelerated during the pandemic, leading to the two most successful Covid vaccines — made by Pfizer and Moderna.

These latest results show further underline that it has promise against cancer. 

‘It’s a tremendous step forward in immunotherapy,’ Eliav Barr, Merck’s head of global clinical development and chief medical officer, said in an interview.

Paul Burton, Moderna’s chief medical officer, said in a separate interview the combination ‘has the capacity to be a new paradigm in the treatment of cancer’. 

Stephane Bancel, Moderna’s chief executive, said: ‘Today’s results are highly encouraging for the field of cancer treatment.

‘MRNA has been transformative for Covid and now, for the first time ever, we have demonstrated the potential for mRNA to have an impact on outcomes in a randomised clinical trial in melanoma.

‘We will begin additional studies in melanoma and other forms of cancer with the goal of bringing truly individualised cancer treatments to patients.

‘We look forward to publishing the full data set and sharing the results at an upcoming oncology medical conference, as well as with health authorities.’

The firms are now seeking to launch phase three trials ‘rapidly’, and expand the drug to other types of cancer.

Previous trials of mRNA shots for cancer showed promise against head and neck cancer, but were not effective for colorectal cancer.

Merck and Moderna will share the production and commercial costs and split the profits if the cancer vaccine goes to market.

As part of the updated deal, Merck will pay $250million to Moderna for joint rights to the cancer vaccine.

The two drug makers have been running trials of the shot together after forming a ‘strategic partnership’ in 2016.

Moderna was able to develop, trial and seal approval of its Covid shot within the space of a year. The vaccine uses DNA taken from each patient’s tumor.

This genetic snippet is then inserted into messenger RNA — the molecule that carries a cell’s instructions for making proteins.

Once inside the body, the mRNA delivers this piece of code to human cells, teaching them to recognize cancer cells and attack them if it returns.

The vaccine is being given in nine doses every three weeks, along with one course of Keytruda every three weeks.

With the Covid vaccine market expected to die down in the near future, Moderna has been turning its attention to non-Covid vaccines.

The American Cancer Society says that the rates of melanoma have been growing significantly over the past years.

It estimates that about 99,780 new melanomas will be diagnosed (around 57,180 in men and 42,600 in women) in the US in 2022.

And about 7,650 people are expected to die of melanoma (roughly 5,080 men and 2,570 women).

You are more than 20 times more likely to get melanoma if you are White compared to if you are African Americans.

The lifetime risk of contracting melanoma is about 2.6 per cent (one in 38) for Whites, 0.1 per cent (one in 1,000) for Blacks, and 0.6 per cent (one in 167) for Hispanics.

The type of cancer is more common in men, but before age 50 it is more prevalent in women. 

Merck and Moderna will share the production and commercial costs and split the profits if it goes to market

The older you are, the more at risk you are from melanoma.

The average age of diagnosis is 65, but it is not unusual in those under 30 either.

It is one of the more common cancers in young adults, particularly young women.

Melanoma occurs after the DNA in skin cells is damaged (typically due to harmful UV rays) and then not repaired so it triggers mutations that can form malignant tumors.

It is currently treated in a few different ways.

The melanoma can be removed by removing the entire section of the tumor or by the surgeon removing the skin layer by layer. When a surgeon removes it layer by layer, this helps them figure out exactly where the cancer stops so they don’t have to remove more skin than is necessary.

The patient can decide to use a skin graft if the surgery has left behind discoloration or an indent.

Immunotherapy, radiation treatment or chemotherapy may be needed if the cancer reaches stage III or IV.

That means that the cancerous cells have spread to the lymph nodes or other organs in the body.

Other trials of the cancer shot have shown it isn’t effective in colorectal cancer patients, but it did show promising results for head and neck cancer.

In the first 10 participants, two had their tumors completely disappear, and a further five had their tumors shrink.

In 2010, the FDA approved sipuleucel-T, a vaccine used to treat prostate cancer that has spread.

But the treatment, available to late stage cancer patients, does not appear to lead to tumors shrinking and only gives men who receive it a few additional months to live.

Studies are now looking to see if the shot can be used in people with prostate cancer at earlier stages.

Dr Stephen Hoge, Moderna’s president, said: ‘We have been collaborating with Merck on personalized cancer vaccines (PCVs) since 2016, and together we have made significant progress in advancing mRNA-4157 as an investigational personalized cancer treatment used in combination with Keytruda.

‘With data expected this quarter on PCV, we continue to be excited about the future and the impact mRNA can have as a new treatment paradigm in the management of cancer. Continuing our strategic alliance with Merck is an important milestone as we continue to grow our mRNA platform with promising clinical programs in multiple therapeutic areas.’

Source: Read Full Article