Lancet Oncology: mRNA cancer vaccines and their clinical progress

The development of mRNA new crown vaccines, from birth to emergency use, takes only a few months, setting a record
for the speed of human research and development of new drugs.
One wonders what else mRNA technology can do
.

Can it still be applied to cancer treatment? As early as 1996, researchers first used mRNA technology to develop cancer vaccines
.
Now, about 30 years later, with the maturity of mRNA technology, mRNA cancer vaccines will not be too far
away.

Recently, four experts in the field of cancer published a review paper in The Lancet Oncology journal, summarizing the current research and development progress and clinical trials of mRNA cancer
vaccines.
To date, at least 35 mRNA cancer vaccines are in clinical development
.

In fact, what the mRNA giants want to tackle most is cancer
.
Previously, BioNTech's founder, U? ur ？ In an interview with the BBC, the Ahins said they had made some breakthroughs in the field of cancer vaccines, and the results would be available
by 2030.
Details: BioNTech founders: mRNA cancer vaccine has achieved a breakthrough and will be available by 2030

What stage has mRNA cancer vaccine research entered? How much hope does it offer cancer patients?

The mRNA vaccine has been an astonishing success, with billions of people around the world receiving the mRNA vaccine
.

But researchers have long hoped to treat cancer with mRNA vaccines and continue to work on the development
of such vaccines.

Recently, Ms.
Inge Marie Svane, Professor of Clinical Medicine at the University of Copenhagen in Denmark, together with three other scientists, wrote a paper revealing the global progress of mRNA cancer vaccine research and development and clinical trial status
.

01

Principles of mRNA cancer vaccines

The preparation of mRNA new crown vaccine, presumably many people have understood, is to let mRNA express the S protein sequence of the new crown virus and human cells, so as to stimulate the human immune response, and then produce antibodies
against the new crown virus.

In fact
, the same is true of mRNA cancer vaccines.
mRNA is used to quickly express cancer antigens, produce antibodies and kill cancer cells
in the body.

Specifically, when an mRNA cancer vaccine enters a human cell, the human immune system starts working
.
The vaccine first instructs human cells to produce proteins, and as long as these proteins are present in intact viral or tumor cells, they can be recognized by antigen-presenting cells such as dendritic cells and presented to T cells to initiate an immune response
.

Mechanism of action of mRNA cancer vaccines

"Dendritic cells are like teachers, educating T cells to learn to search for cancer cells and respond immunely.
"
Dr.
Karine Breckpot, who studies mRNA vaccines at the Vrije Universiteit Brussels, Belgium, uses a metaphor to explain the role
of dendritic cells.

Although the biological principles of mRNA tumor vaccines are universal, various types of mRNA tumor vaccines have different performance in clinical trials
.
So, what mRNA tumor vaccines are there? How is their development progressing?

02

Clinical trial progress of mRNA tumor vaccine

At present, there are three major types of mRNA tumor vaccines in the clinical trial stage, namely: naked mRNA cancer vaccine, prepared mRNA cancer vaccine and dendritic cell vaccine
.

1.
The bare mRNA vaccine does not have a shell, and the clinical trial progress of this vaccine is the fastest, and it has been carried out in the late stage of clinical trials, and it must not be too far
from the market.
Because bare mRNA is easily degraded by extracellular RNases, the researchers developed several prepared mRNA cancer vaccines
with nanocarriers.

Schematic diagram of the principle of an mRNA cancer vaccine

2.
At present, there are two forms
of protamine-encapsulated mRNA cancer vaccine and mRNA lipid complex vaccine.
Among them, protamine-encapsulated mRNA cancer vaccines show a high safety profile, but the effect is not particularly significant
.

3.
Among the many mRNA tumor vaccines, mRNA-dendritic cell cancer vaccine has attracted special attention
.
Because this vaccine can not only cause an immune response, but can also be used to control and regulate the type of
immune response.
However, the development of mRNA-dendritic cell cancer vaccines may be slower than other types of mRNA cancer vaccines, because obtaining the source of dendritic cells and performing ex vivo manipulation of dendritic cells is laborious and time-consuming
.
Perhaps this will affect the availability of vaccines
.

Overview of clinical trials of mRNA tumor vaccines

Clinical trials of mRNA-dendritic cell tumor vaccines

Interestingly, based on trial results published over the past 5 years, mRNA-dendritic cell cancer vaccines can prevent or delay disease recurrence and potentially prolong patients' lives
.

Overall, we can see that the number of clinical trials of various mRNA cancer vaccines is increasing rapidly, providing a new reference for diagnosis and treatment protocols
.

So, how many more steps do we need to take before these mRNA cancer vaccines can truly benefit cancer patients?

03

Hope and challenge

At present, several clinical trials have greatly promoted the research and development process of mRNA cancer vaccines, but they still face many challenges and problems
.
In addition, researchers are also tapping into the potential
of this cancer vaccine.

When developing an mRNA cancer vaccine, scientists are still thinking about the possibility
of preventing problems before they occur.
Most mRNA cancer vaccines are for treatment, not prophylaxis
.

Personalized mRNA cancer vaccines are also in
the process of being developed.
Moderna sponsored a clinical trial to test a personalized vaccine
in patients with advanced head and neck cancer.

The preparation of mRNA cancer vaccines still faces great challenges, and mRNA cancer vaccines cannot yet identify tumor-specific mutations or inconsistent sequences
.
How to optimize the function of mRNA cancer vaccines is still a difficult problem
for researchers.

However, the future of mRNA cancer vaccines is promising
.
While clinical trials of many mRNA cancer vaccines are still in the early stages of research, the field is evolving
rapidly.

It is believed that in the near future, more mRNA cancer vaccines can be developed, and the delivery of mRNA cancer vaccines can also be optimized and applied to the diagnosis and treatment of different tumors to prolong the lives
of patients.