バイオテクノロジーでがんと闘う – mRNAワクチンが画期的な理由

mRNA革命

When the COVID-19 pandemic struck, the world’s medical community initially prepared for a disaster of the scale of the Spanish Flu, which struck during WW1 and killed 50 million people (from a much smaller global population). Instead, “only” 7 million people are considered to have died from Covid.

mRNAワクチンは、当時としては新しい技術であり、パンデミック中/以降に非常に迅速に展開されました。従来のワクチン技術と比較してmRNAワクチンがユニークだった点は、開発のシンプルさです。従来のワクチンは、ウイルス粒子を不活化または弱体化させる正確なプロトコルを見つけ、ウイルスがどのように病原性を持ち、免疫系がそれをどのように検出するかを解明し、実際に機能するかを確認するために数か月または数年のテストが必要でした。

mRNAワクチンは、代わりにウイルスゲノムを直接見ることができ、これはCOVID-19が発見された最初の週に取得されたデータです。そして、ウイルスの一部に対応するmRNA配列を作成し、患者の体内でそのタンパク質を産生させます。

この方法により、免疫系はウイルスタンパク質に直接反応することを学び、実際のウイルスに曝露されたときにすぐに活性化できるようになります。

出典: ESCO Life Sciences

ウイルスの発見からワクチン作成までのプロセスが数週間で完了し、主にゲノムデータに基づいているため、これは「医学のためのコードを書く」ことに例えられ、従来の時間のかかるバイオリサーチに比べて格段に速いとされています。

This creates hope that other diseases that have been resistant to vaccination so far could be prevented with mRNA vaccines. For example:

• Moderna is working on mRNA vaccines for RSV, EBV (mononucleosis), HSV (herpex), VZV (varicella), HIV, norovirus, Lyme disease, Zica, Nipah, and mPox vaccines
• BioNTech  is working on mRNA vaccines for HSV, tuberculosis, malaria, mPOX, and shingles
• Curevac also works on mRNA vaccines for bird flu, Lassa yellow fever, RSV, rabies, malaria, and rotavirus.

感染症を超えて

As the mRNA vaccine works by training the immune system to focus on a given target, determined by its genetic sequence, it can theoretically be trained to attack any type of specific protein, not just infectious diseases.

We also know that cancer cells display specific markers absent in healthy cells. This is the basis of all cancer immunotherapies, like for example CAR-T therapies and monoclonal antibodies, which we discussed in “Monoclonal Antibodies: The Original Precision Therapy”.

The issue is often properly to train the immune system to detect these cancer cells, as custom manufacturing of antibodies of immune cells in labs is expensive and hard to scale up.

This is exactly what mRNA-based cancer therapy is looking to achieve. And progress is being made quickly.

mRNA肺がん臨床試験

At the end of 2024年8月, mRNA vaccine leader BioNTech (BNTX ) (producer of the “Pfizer (PFE ) vaccine”) announced that it started global clinical trials in 7 countries and 34 research sites for a mRNA-based lung cancer vaccine, called BNT116.

The focus will be non-small cell lung cancer (NSCLC). It will involve around 130 patients, who will receive BNT116 in combination with immunotherapy, with the goal to boost the efficiency of the treatment.

The trial will enroll patients at different stages of NSCLC, from early-stage disease before surgery or radiotherapy (Stage 2 and 3) to late-stage disease (Stage 4) or recurrent cancer.

It is a more complex therapy than mRNA vaccines like the Covid-19 vaccines, as it includes six consecutive injections five minutes apart over 30 minutes, with each jab containing different RNA strands. The patient will then go on to get the vaccine every week for six consecutive weeks, and then every three weeks for 54 weeks.

再発抑制

A key expected effect of the mRNA treatment is to reduce the re-occurrence of cancer once the treatment is done, as the effects are expected to be much more lasting than with classical immunotherapies.

This is because the “trained” immune cells will stay active and vigilant against the cancer market, the same way they would be against the risk of a future infectious disease attacking the body.

This also means that while the treatment is not preventing cancer, if it works, it will truly deserve the “vaccine” qualification, at least against cancer re-occurrence.

その他のmRNA応用

Because of its versatility in leveraging the immune system, mRNA technology could be used for a variety of ailments beyond infectious diseases and cancers.

Among the various possible applications, we can mention:

• Rare diseases and genetic diseases: including cystic fibrosis and phenylketonuria.
• Diagnostics: as cancer cells express different protein profiles than normal ones, their mRNA coding for these proteins also differs. This can open the way for cancer detection through a technique called liquid biopsy.
  • Such diagnostic tools will allow for early cancer detection, dramatically increasing the survival rate.
• Heart attacks and healing damaged organs: Researchers at Penn Medicine are using mRNA to modify liver genes and reduce heart attack risks. They are also working on a cure for fibrosis in the heart tissues, a major cause of heart failure.
• Safer gene therapies: While most gene therapies look to insert DNA into cells or to modify DNA using CRISPR technology, this can have unintended consequences as the insertion is permanent.
  • For more transient effects that still rely on gene therapy, injection of mRNA into cells can be used, although this technique is still very recent, and appropriate mRNA delivery systems have only been developed in the last few years.
• Auto-immune diseases: mRNA vaccine can be used to reduce instead of stimulate the immune system response, which is required in auto-immune diseases, where the body attacks healthy cells.
  • This can be achieved by inducing the proliferation of Regulatory T cells (Treg), which reduce the intensity of the erroneous immune reaction.

mRNAのリスク

After the quick emergency unrolling of the mRNA vaccine during the pandemic, many feared that it was actually causing plenty of unintended side effects, like heart inflammation (myocarditis).

Combined with the politicization of the vaccines and the chaos of lockdowns and the pandemic, this has led to a lot of confusion.

A few years later, we are now starting to get strong data. While rare, the cases of myocarditis are real, and according to the CDC, “have most frequently been seen in adolescent and young adult males within 7 days after receiving the second dose of an mRNA COVID-19 vaccine”.

Further research from 2024年9月 indicates that the interval between the vaccine and booster shot might be an important factor:

“We show that longer intervals between each consecutive dose, including booster, may decrease the occurrence of vaccine-associated myocarditis by up to a factor of 4, especially under age 50. These results suggest that a minimum 6-month interval might be required when scheduling additional booster vaccination.”

Influence of mRNA Covid-19 vaccine dosing interval on the risk of myocarditis

– Nature Communication

So overall, mRNA, like most treatments, is never 100% without side effects.

However, when it comes to new applications, like aggressive and re-occurring lung cancers, the risk of side effects can likely be negligible compared to the increased survival rate.

mRNAワクチンへの投資

mRNA has become, in large part due to the pandemic, a darling of investors in 2020-2022. The necessary cooling down of mRNA vaccine sales post-pandemic has caused the prices of many mRNA-related stocks to decline as a result.

This does not change the fact that technology is remarkably powerful in preventing diseases, from infectious diseases to cancer, and maybe rare diseases, auto-immune syndromes, etc. And the company’s expertise in mRNA vaccines gives it a serious headstart in bringing this tech to new fields of medicine.

You can invest in mRNA companies through many brokers, and you can find here, on securities.io, our recommendations for the best brokers in the USA, Canada, Australia, the UK, as well as many other countries.

If you are not interested in solely mRNA companies, you can also look into biotech ETFs like WisdomTree BioRevolution UCITS ETF (WBIO) (WT ), VanEck Biotech ETF (BBH), or First Trust NYSE Arca Biotechnology Index Fund (FBT), which will provide more diversified exposure to capitalize on the growing biotech economy.

mRNAソリューションを提供する企業

One of the leading companies in mRNA cancer therapies is BioNTech, which is building from its success in developing the mRNA vaccine commercialized by Pfizer.

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BioNTech currently has 11 different candidates in cancer treatments, covering cancer in the ovaries, prostate, intestines, skin, head, neck, and multiple solid tumors.

Most oncology treatment clinical trials are in phase 1/2, with already three candidates in phase III.

出典: BioNTech

In total, the company has 21 clinical programs in oncology. This includes not only mRNA, but also small molecules, Immuno-Oncology agent (IO), and Antibody-drug-conjugates (ADCs).

The first oncology product is expected to be potentially launched in 2026.

出典: BioNTech

感染症

BioNTech also stayed the leader in COVID-19 vaccines, with >50% market share, and upcoming combination respiratory vaccines (Covid + Flu/Influenza) in late 2025 or 2026 if approved.

Regarding infectious diseases, BioNtech is pursuing vaccines for shingles, Herpex, tuberculosis, malaria and Mpox. Among those, the diseases affecting the most people are Herpex viruses (3.7 billion people infected), malaria (249 million), and tuberculosis (10.6 million).

出典: BioNTech

AI

BioNTech is also very active in the AI-Biotech field, with the creation in 2020 and full acquisition in 2023 of the company InstaDeep AI.

出典: BioNTech

InstaDeep is the “first AI Immunotherapy Platform”, using LLM technology on DNA and protein sequences, AI vision for histology (tissues under a microscope) analysis, and AI agent for lab automation and quality control.

The goal is to deploy AI across the entire R&D pipeline.

It uses a supercomputing cluster with 224 Nvidia (NVDA ) H100 GPUs and 86,000 CPU cores, with 0.5 ExaFLOPS, making it into the top 100 worldwide. InstaDeep’s genomics AI models are among the most downloaded, illustrating how they are “state-of-the-art” in this field.

財務情報

The money from the pandemic gave the company a very strong position, with €16,9B in total available cash by mid-2024. In 2023, Covid-19 vaccines still generated €3.8B in revenues, for a gross profit of €3.2B.

This is likely to slow down in 2024, but overall, the company has very strong finances for what is still ultimately an early-stage biotech startup with only one product commercialized.