Novel Immunotherapy
Most modern cancer therapies aim to train the body’s immune system to detect and attack cancer cells efficiently. This method even won the 2018 Nobel Prize in Medicine (see the link for more information).
It can be done with now-established therapies like CAR-T therapies or maybe soon experimental treatments like mRNA vaccines against specific cancers, which are making quick progress with clinical trials for mRNA against lung cancer.
However, this is not the only possible way to encourage the immune system to target cancer cells. Researchers at Columbia University, New York, have modified bacteria to attack cancer. They published their findings in the prestigious publication Nature under the title “Probiotic neoantigen delivery vectors for precision cancer immunotherapy.”
Using Bacteria Against Cancer
The idea is not new; in the 19th century, it was noticed that injecting bacteria into a tumor could cause it to shrink. Today, early-stage bladder cancers are treated with bacteria. The mechanism behind it is that bacteria can prosper in the oxygen-deprived environment of tumors and locally provoke an immune response that attacks both the bacteria and the cancer cells.
The issue is that such an undirected process is often not enough to help with cancer therapy. So, the bacteria have to be modified for maximum efficiency.
Customizing Bacteria For Cancer Detection
The central concept is to make the bacteria express markers specific to cancer cells. These “neoantigens” are proteins that cancer cells produce but normal cells do not.
By having the bacteria carrying these proteins, the immune systems detect them and start attacking anything carrying them, both bacteria and cancer cells.
This has a solid advantage over the type of immunotherapy, as the bacteria-induced reactions activate a wide variety of different immune cells. So it involves NK cells, lymphocytes CD4+ and CD8+, macrophages, antigen-presenting cells (APC), etc.
Reducing Immunity Suppression
This wide stimulation of the immune system creates an important effect missing in all previous variants of tentative cancer vaccines: canceling immune response suppression.
Most cancers are able to reduce the intensity of the immune response in the vicinity of the cancer. So even if in theory the body contains lymphocytes able to detect and kill the cancer cells, in practice they are not activating the way they should.
By activating many other immune system cells at the same time as it “trains” the lymphocytes, the bacteria greatly reduce the immune response suppression.
Personalized Cancer Therapy
The first step is an accurate genetic sequencing of the cancer cells. This way, the researchers (and in the future doctors) are able to identify in every way how cancer cells differ from normal cells and create a large database of neoantigens.
These potential neoantigens are then selected so that the ones most likely to trigger an immune response are added to bacterial plasmid (a circular DNA, like a mini chromosome). This plasmid is then inserted in the bacteria, so it starts producing the neoantigens.
Source: Nature
Because the starting point is the specific antigen to the patient’s cancer, this creates a personalized therapy. Instead of a catch-all therapy hoping it will work for this cancer in particular, it is designed from the ground up to target this cancer in particular.
Multi-Antigen Therapy
This method also brings another step forward in immunotherapies relying on cancer neoantigens. Instead of focusing on one specific cancer marker, it adds to the bacteria a whole series of neoantigens.
This could solve another problem that often leads to failure in cancer therapy: cancer mutation.
Cancer cells are extremely unstable genetically, which is the cause of the cancer in the first place. This means that a cancer is often actually composed of a wide variety of mutations and abnormal cells instead of just one specific type.
This is an issue for therapies addressing a specific cancer marker. Even if the therapy successfully eradicates all cancer cells carrying this marker, a small percentage that does not might survive. This can lead the cancer to lose the targeted neoantigen, making the therapy ineffective.
This bacteria-induced therapy uses many neoantigens at once, greatly reducing the chance of the cancer losing all neoantigens all at once.
“Because our platform allows us to deliver so many different neoantigens, it theoretically becomes difficult for tumor cells to lose all those targets at once and avoid the immune response.”
Dr. Nicholas Arpaia – Associate professor of microbiology & immunology at Columbia University.
Combined with the removal of immune response suppression, this could make the therapy a lot more powerful and likely to fully eradicate the cancer, instead of just weakening it.
When testing on mice, a treatment using bacteria expressing 19 and then 42 neoantigens fought cancer very effectively.
Source: Nature
Turning The Bacteria In Neoantigen Factories
While already impressive, these breakthroughs were not the only work the researchers put into the project. They also modified the bacteria so they would induce an immune reaction as strongly as possible. To do so, they removed from the bacteria its own mechanism that helps it evade the immune system. They are more likely to be eaten by immune cells, more visible to them, not able to create biofilms, etc. This creates a much stronger immune response against the bacteria and, therefore, against the cancer neoantigens.
It is also a safety measure, as this way, the bacteria are unable to multiply and are quickly recognized and eliminated by the immune system. So they are not in danger of creating an infection, something that would be very dangerous for already weakened cancer patients.
They also genetically modified the bacteria so that it is missing some protease enzymes in charge of degrading proteins. This way, they express even more of the neoantigens. This should be a strong basis for further development of this method, with the modified weakened bacteria a perfect platform for more research.
Timing
The only potential issue with this method is that it needs to start with a complete genomic and transcriptomic analysis of the cancer. So the time-to-treatment will depend on on how long it takes to sequence the tumor. With fast growing cancers, this could make the difference between life and death.
Luckily, this is something that has become a lot faster in recent years, thanks to great progress in genomics and “multiomics“, itself built on quick progress in semiconductors and laser technologies. It also made such analysis a lot cheaper.
So the results that a few years ago would have been interesting, but mostly theoretical due to the required time and budget, could be deployed with human patients today.
Interestingly, the time to modify the bacteria is actually less of an issue. Genetic engineering of bacteria can be quite fast, and potentially faster than what it takes to create other forms of vaccines.
“The time to treatment will first depend on how long it takes to sequence the tumor. Then we just need to make the bacterial strains, which can be quite fast. Bacteria can be simpler to manufacture than some other vaccine platforms,”
Dr. Tal Danino – Associate professor of biomedical engineering at Columbia’s School of Engineering.
Cancer Prevention?
Because the immune system “training” is so encompassing with dozens of antigens, it is likely that this type of immunotherapy could have much more lasting effects, including against reoccurrence and metastases.
A more intriguing effect was detected, and this treatment apparently could also potentially help prevent cancer.
Once activated by the bacterial vaccine, the immune system would be prompted to eliminate cancer cells that have spread throughout the body and prevent further metastatic development.
“The bacterial vaccine also reduced the growth of cancer when administered to mice before they developed tumors and prevented regrowth of the same tumors in mice that had been cured.”
Dr. Tal Danino – Associate professor of biomedical engineering at Columbia’s School of Engineering.
This would likely be less effective, as it would only act on cancer developing in the future the neoantigens that have been prepared in advance. So, other cancers would still develop and need personalized treatment.
Still, it is an intriguing idea and likely to be the focus of further research in the future.
Investing In Cancer Therapies
Cancer therapies are growing to be one of the largest medical markets, valued at $205B and expected to grow 12.4% CAGR to $466B by 2031.
It is likely that several new disruptive technologies will improve cancer survival rates in the near future, including early detection with liquid biopsies, mRNA cancer vaccines, etc.
You can invest in cancer 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 specific cancer-related companies, you can also look into biotech ETFs like WisdomTree BioRevolution UCITS ETF (WBIO), 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.
You can also check our articles “Top 10 Cancer Therapy Stocks” and “Best Early Cancer Detection And Liquid Biopsy Stocks”.
BMS is a company with a long-established presence in oncology, which was reinforced by the acquisition of Celgene in 2019. In October 2023, it also acquired Mirati Therapeutics for $5.8B (an all-cash transaction, through cash and debt), accessing the company’s portfolio of lung, liver, and pancreatic cancer therapy.
Bristol-Myers Squibb Company (BMY -0.26%)
BMS’s R&D effort combined with this acquisition has strongly boosted the company’s portfolio, with its new products growing rapidly, more than tripling since 2021. The “in-line brands” have also grown by 7% year-to-year.
Source: BMS
The company’s R&D pipeline is dominated by oncology, as 50 out of 71 therapies in development are targeting cancer, with a focus on solid tumors, lymphoma, and myeloma.
Overall, we could say that the company’s focus on immunology and oncology has paid off, with good results from the R&D efforts. It also feeds the company’s pipeline by providing it with a deep understanding of the cause of cancer and possible targets it can aim towards for new therapies.
It is also expanding the possible application of its existing drugs, for example, Opdivo, the initial CTLA-4 drug, was newly approved in 2024 for “First-Line Treatment of Adult Patients with Unresectable or Metastatic Urothelial Carcinoma”.
This oncology focus also pays off in terms of manufacturing, with new therapies requiring advanced facilities to produce custom cell lines and/or monoclonal antibodies.
Besides cancer, BMS also saw in September 2024 the approval of Cobenfy, the first new mechanism in decades for the treatment of schizophrenia in adults (1.6M people in the US). The launch of Cobenfy out of the US is expected to lag behind by 3 years.
BMS has been rising quickly since 2018 and has become one of the leading companies in oncology. This position will likely persist for the next few years and be highly profitable for its shareholders.
