December 8, 2022

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Will the mRNA vaccine that can cure cancer come out near soon?

Will the mRNA vaccine that can cure cancer come out near soon?



Will the mRNA vaccine that can cure cancer come out near soon?

“Cancer vaccines based on mRNA technology may be available as soon as 2030,” Professor Uğur Şahin and Özlem Türeci, co-founders of German biotechnology company BioNTech, told the BBC recently.

After the relevant news was reported by media, it quickly entered the hot search.

A large number of comments say that vaccination and cancer prevention will be one of the greatest inventions in modern times.

But this high hope is a misunderstanding.

According to information from the Dana-Farber Cancer Institute in the United States, base on mechanism of action, existing cancer vaccines are divided into two categories: 

One is to prevent viral infection and prevent cancer. The “representatives” include the marketed HPV vaccine and hepatitis B virus vaccine.

The second is the “therapeutic vaccine” vaccinated after the occurrence of cancer, which aims to activate the immune system and kill cancer cells in a targeted manner, which belongs to the category of immunotherapy.

The mRNA cancer vaccine mentioned in the news is a therapeutic vaccine. It is different from the anti-cancer vaccine currently recognized by the public in terms of preparation process and mechanism of action.

“Related research and development has been developing slowly for more than 20 years.” The “Pharmaceutical Journal”, a subsidiary of the Royal Society of Pharmacy, published an article in August this year, saying that the development of cancer vaccines based on mRNA is still a frontier field, “just beginning.”

Will the mRNA vaccine that can cure cancer come out near soon?
 Prof. Uğur Şahin (left) and Prof. Özlem Türeci, co-founders of German biotech company BioNTech. /BBC


How can “vaccines” still cure diseases?

According to BioNTech’s official website, the company currently has 14 mRNA cancer vaccines in clinical research, covering melanoma, rectal cancer, head and neck cancer, solid tumors and other cancer types.

Some show encouraging results.

At the 2022 American Society of Clinical Oncology Annual Meeting (ASCO) , the division announced positive Phase I results for the cancer vaccine BNT122.

The data show that the combination of BNT122, PD-L1 blocker and chemotherapy in pancreatic cancer patients undergoing surgical resection has high safety and good efficacy.

50% (8/16) of patients were relapse-free after 18 months.

“Pharmaceutical Journal” pointed out that mRNA technology can deliver the genetic genes of specific tumor antigens to the human body, induce cells and produce antibodies, thereby activating the immune response, and searching, attacking and destroying cancer cells throughout the body. This process makes full use of the principle of human immunity, or the reason for its name “vaccine”.

Once awakened, the immune system also retains long-term memory of abnormal antigens, allowing it to act again when the cancer recurs

. BioNTech’s study of some patients undergoing long-term immune monitoring found that some responders had memory T cells, as well as helper and cytotoxic T cell responses.

Moderna, which also occupies the high ground of mRNA technology , also has a number of therapeutic cancer vaccines under development.

On October 12, local time this year, Moderna announced that it will cooperate with the pharmaceutical company Merck to jointly develop and sell a product.

In 2019, Moderna initially disclosed the phase I data of the mRNA cancer vaccine combined with Merck’s anti-PD-1 drug pembrolizumab, claiming that the control rate of malignant tumors was 90%. This exceeded many of the drugs on the market at the time.

On October 1 this year, “The Lancet-Oncology” published a review saying that mRNA therapeutic cancer vaccines have many advantages.

Including good tolerance, no risk of genome integration, no infectivity, easy to degrade, easy to activate and maintain humoral and cellular immunity, short production cycle and low production cost.

The article pointed out that there are a total of 17 related clinical studies registered with ClinicalTrials.gov.


How hard is it to develop?

Therapeutic cancer vaccines are not new. To be precise, it is a tumor immunotherapy that entered research and development relatively early.

In April 2010, the world’s first related drug , Provenge, was approved for marketing in the United States.

The drug extracts the dendritic cells (DC) of the patient’s own immune cells, which are activated in vitro and then infused back for the treatment of asymptomatic or mildly symptomatic prostate cancer.

It doesn’t subvert the clinic. Approved data show that compared with the control group, Plevir can prolong the median overall survival by 4.1 months. In 2012, the oral androgen receptor inhibitor enzalutamide was launched in the United States.

A study by the Chinese University of Hong Kong showed that, as a second-line treatment, enzalutamide could prolong the median overall survival by 15.8 months; as a third-line and above treatment, it was up to 7.4 months.

The price of Prevail is high, the treatment plan is complicated, and it is also very persuasive to dismiss doctors and patients.

According to data released by the American Society of Clinical Oncology’s Genitourinary Cancer Symposium (ASCO-GU 2020) in 2020 , about 30,000 male patients have been prescribed Plevis in the past 10 years. During the same period, about 190,000 new prostate cancer patients were diagnosed in the United States each year.

There are even more therapeutic cancer vaccines that are “throwing on the street” in the research stage. Including brain cancer vaccine Rintega, pancreatic cancer vaccine algenpantucel-L and so on.

Some analysts pointed out that the unsatisfactory research results are largely due to the diversity of cancer cell antigens, the ability of cancer cells to escape immunity, and insufficient immune responses.

At present, there are dozens of therapeutic cancer vaccines under development in the United States with different technical paths and cell sources. Its mechanism of action is similar to that of mRNA cancer vaccines: the use of a certain cancer cell analog causes an immune response and creates an immune memory.

But no matter which technology is used, the first and crucial step is to identify meaningful cancer cell antigens and let them exercise the immune system. In this way, cancer vaccines can only target cancer cells without harming healthy tissue.

Finding specific antigens is not enough. Each cancer patient is “unique”, especially in its antigen presentation characteristics and immune activation capabilities.

If a general cancer vaccine is studied, the efficacy of different patients varies. This will increase the difficulty of research and development.

In addition, cancer cells are good at camouflage and can evade detection and attack by the immune system by mutating and changing surface proteins. This could affect the effectiveness of cancer vaccines.

According to comprehensive media reports, finding the most feasible way of drug administration and the lack of strong lethality to tumors are also problems that need to be solved in the future.

Some scientists have suggested that with the improvement of tumor treatment technology, the application scenarios of therapeutic cancer vaccines may be limited in the future.

In the next decade, tumor treatment technology will face major changes, and therapeutic vaccines may be lost due to the rapid development of oncolytic virus therapy technology. Part of the value, the applicable scenarios will also be limited.

Time is the biggest enemy of R&D. Taking mRNA therapeutic cancer vaccines as an example, several products that are emerging at this stage are mostly in Phase II clinical trials. According to the aforementioned “Lancet-Oncology” article, only one has entered Phase III.

The BBC quoted the founder of BioNTech as saying that he is cautious about the development of therapeutic cancer vaccines.

“Through the development and industrialization of the COVID-19 vaccine, BioNTech has better understood how the human immune system responds to the mRNA vaccine. The urgent development and promotion of the COVID-19 vaccine has also exercised the administrative capabilities of the drug regulatory authorities. These can accelerate the future The launch of a cancer vaccine.”

Even if mRNA vaccine technology is approved for cancer treatment, it does not mean that it can completely replace other standard treatments. Just like PD-1, surgery is the only cure for most early-stage solid tumors, at least for now. In the field of cancer treatment, each treatment method has its advantages and disadvantages, and comprehensive use is the most critical.

References:
[1] BioNTech: Could Covid vaccine technology crack cancer?.BBC
[2]Can mRNA Vaccines Help Treat Cancer?.NIH
[3] Clinical advances and ongoing trials of mRNA vaccines for cancer treatment. The Lancet Oncology. VOLUME 23, ISSUE 10, E450-E458, OCTOBER 01, 2022.doi.org/10.1016/S1470-2045(22)00372-2
[4]How close are we to developing an mRNA cancer vaccine?.pharmaceutical journal

Will the mRNA vaccine that can cure cancer come out near soon?

(source:internet, reference only)


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