The optimism sparked by the covid mRNA vaccines fueled hopes for the discovery of a cancer vaccine in the near future. However, the search of a cancer vaccine isn’t new at all, indeed even before covid, mRNA vaccines were under clinical investigations for the treatment of melanoma.

An early-stage study from $BNTX (BioNTech SE-ADR) and Roche’s subsidiary Genentech published in Nature in 2017 showed promising results in patients affected by this disease. Other types of vaccines have been tested even earlier than that, but with little success. Since then, other companies joined the race for cancer vaccine. However, accomplishing this goal will require something more and probably involve multiple companies and technologies.

Here, I would like to give you a brief overview of this field, and my personal opinion about the technologies and companies that will a key role in accomplishing this goal. The overall idea of cancer vaccine is similar to Sars-cov-2 vaccine, but the RNA that codifies the spike protein will be replace with the RNA of proteins that are usually mutated in cancer cells which take the name of neoantigens. This in principle can trigger a cancer specific immune response.

Both $MRNA (Moderna Inc) and $BNTX are now working on two major type of cancer vaccines: shared antigen vaccines and personalized cancer vaccines.

Shared antigen vaccines

Shared antigen vaccines are vaccines that utilize neoantigens that are commonly appearing across multiple individuals with the same cancer type.

This approach relies on the assumption that the neoantigens used are present in all patients, but given the high diversity of cancer from patient to patient this might not be the case. In order to increase the chance that patient will respond to the vaccine, shared antigen vaccines usually contain a cocktail of different neoantigens. Despite that, I still believe the number of patients that can benefit from shared antigen vaccines will be a limited subset.

Personalized cancer vaccines

Personalized cancer vaccines use a much more advanced approach. First a patient’s sample is collected, and DNA sequencing is used to identify patient specific neoantigens. Next, the neoantigen RNA is loaded into the lipid nanoparticle and delivered to the patient. The study I mentioned above is using personalized cancer vaccines.

Last year, phase 1 clinical trial from $BNTX and $ROG.ZU (Roche Holding Ltd) didn’t show any benefit for the patient, but in that trial the vaccine was applied on late stage and heavily treated patients. Phase 2 clinical trial started this year.

This second approach solve the problem of the diversity of neoantigens in cancer patients, but it makes the manufacturing process much more complicated and expensive.

Challenges

Heterogeneicity

The problem of tumor heterogeneity doesn’t stop at the difference from patient to patient, but also within the same patient there can be cancer cells carrying different neoantigens and they can be responsible of developing resistance to the vaccine. Therefore, studying this heterogeneity at the single cell level will be an important step toward a cancer vaccine. $TXG (10X Genomics Inc) is one of the leading biotech in single cell technology. Furthermore, DNA-sequencing companies such as $ILMN (Illumina) and $PACB (Pacific Biosciences of California Inc) will also be essential for the characterization of neoantigens.

Immune evasion

Another challenge that will require the integration of other technologies is the immune evasion. Differently from virus, cancer has multiple strategy to evade or repress an immune response. The most common example of this is when cancer cells overexpress a molecule called PD-L1 that works as an inhibitor for immune cells. Luckily, we already have the solution for that. $MRK (Merck & Co.) $ROG.ZU and $AZN.L (AstraZeneca) already commercialized antibodies that block the inhibition of immune cells. These will likely be used in combination with cancer vaccines.

Another way cancer can evade immune system is by depleting the HLA protein which is essential to trigger an immune response. Currently there is not any approved solution for this, but in principle it can be solved with gene editing technologies @CRISPR-Tech. The biopsy needed for identifying neoantigens might also be replaced by liquid biopsy from $GH (Guardant Health Inc) and $EXAS (Exact Sciences Corp), basically extracting tumor DNA coming from dying cancer cells directly from blood.

Data storage

Last but not least, storing and analyzing large amount of genetic information to identify patient’s neoantigen will require large amount of computational power, thus even cloud technologies such as $MSFT (Microsoft) and $AMZN (Amazon.com Inc) will become an important component of this cancer vaccine pipeline.

Summary

The development of effective cancer vaccine will require a combination of multiple technologies involving multiple companies not just in the healthcare industry in order to overcome the complex challenges listed above.

My personal opinion is that if you want to gain exposure to cancer vaccines you should invest into multiple stocks or biotech etfs like $XBI, $XLV, $ARKG or copy portfolio like @Vaccine-Med Furthermore, mRNA vaccines from $MRNA (Moderna Inc) and $BNTX (BioNTech SE-ADR) are not the only vaccine technologies that can be used for the development of a cancer vaccine.

$HTBX is also creating a cell-based vaccine that can deliver cancer neoantigens to the patient, and I’m expecting to see more vaccines like this in the future.

Extra information

Extra point on mRNA vaccines: many of today’s drug are antibodies. mRNA vaccines can be used to produce therapeutic antibodies directly inside your cell. This would open a completely new way of manufacturing drugs.

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