mRNA Cancer Treatment-The Scientific Triangle

mRNA Cancer Treatment of BioNTech Proceeds to Human Trials

BioNTech’s mRNA cancer treatment has taken a new turn. The mRNA cocktail’s success in various mouse models of cancer has encouraged human trials. Find out more on the study and what is in the pipeline from this blog.

BioNTech, a German biotechnology company, is ushering us towards a new era of mRNA cancer treatment.  Already famous for developing the mRNA Covid-19 vaccine with Pfizer, BioNTech’s research is ready to progress to conducting mRNA cancer treatment trials on humans.

BioNTech’s research team has designed a cocktail of mRNAs that can be used as mRNA cancer vaccines. The treatment with the mRNA mixture produced substantial results in the mouse models of colon cancer and melanoma. When combined with the checkpoint inhibition, it produced even better results. The study has been published in the scientific journal Science Translational Medicine.

Scientists began exploring mRNA-based anticancer vaccination and therapeutic approaches about 25 years ago. The renaissance of mRNA cancer immunotherapy happened again recently. mRNA cancer drugs can become an off-the-shelf potent immunotherapeutic tool to combat cancer. Let’s explore the mRNA cancer immunotherapy study conducted by BioNTech further. 

mRNA cancer treatment study conducted by BioNTech

Messenger RNA molecules can attack cancer cells by prompting the body cells to make proteins. Scientists have developed a mixture of mRNA that could instruct the patient bodies’ immune cells to produce cytokines. Cytokines are already naturally produced in the body by T lymphocytes, B lymphocytes, macrophages, mast cells, endothelial cells, fibroblasts, and stromal cells.

mRNA drugs and vaccines can boost cancer-specific T cells besides inducing immunological memory to prevent metastasis and relapse. The best part is that it can be administered via various routes and can be mass-produced.

Details of the research:

The study conducted on multiple mouse models of colon cancer and melanoma showed that the mRNA cocktail upon delivery to the target cells could instruct them to produce anticancer molecules. This helped suppress tumours, and the data obtained from the study supported further development of the cytokine-encoded mRNAs.

The mRNA encoding four cytokines identified as mediators of tumour regression – interleukin-12 (IL-12) single chain, interferon-alpha, granulocyte-macrophage colony-stimulating factor, and IL-15 sushi was delivered by intratumoral injections in mice. These cytokines produced robust anti-tumour responses and tumour regression in the mice.

The administration of the saline-formulated mixture of four mRNAs in a group of 20 mice showed significant tumour suppression. Not only this, but the mRNA mixture brought about complete regression in 17 mice in a time span of 40 days. Further, when the mRNA mixture was administered in combination with either anti-CTLA-4 or anti-PD-1 checkpoint inhibitors, it increased the regression speed.

Additionally, in some mice, it was also observed that the therapeutic molecules travelled from the targeted cancerous cells of the skin to distant lung cancer cells and displayed an anti-tumour response. This suggests that mRNA cancer treatment can be a powerful weapon against the most complicated aspect of cancer treatment – metastasis.

Effective anti-tumour activity was also accompanied by intratumoral IFN induction, increased granzyme B+ T cell infiltration, systemic antigen-specific T cell expansion, along with the formation of immune memory.

The success of the study on the mice model paved the way for phase one/two human trials. BioNTech and Sanofi have come together to carry out the phase 1 basket trial of the mRNA cancer drug called SAR441000. Human trials on patients with solid tumours have been ongoing since 2019 in 231 participants. In the trial, the mRNA mixture is being tested as monotherapy and also in combination with Libtayo.

Libtayo (cemiplimab-rwlc) is a PD-1 inhibitor introduced by Regeneron Pharmaceuticals and Sanofi-Aventis. Preliminary results of mRNA cancer treatment trials on humans released in November 2020 indicated no severe adverse effects.

Key hurdles of mRNA cancer treatment in the past

When it comes to creating cancer vaccines or anticancer therapies, the primary challenge has always been to deal with the numerous ways cancer cells use to evade the body’s immune system. Tumour cells have the uncanny ability to create microenvironments around themselves that can avoid immune responses. So, choosing the right antigen is the biggest hurdle in the case of anticancer treatment agents.

Another potential problem is dealing with the rapid mutations in cancerous cells. So, even if a vaccine can target multiple antigens, it is not certain that the immune system will respond to it.

This is why researchers are now pursuing the novel approach of using neoantigens. Neoantigens are antigens forming on mutating tumour cells.

Researchers have been exploring immunotherapy for a long time but targeting the drug always posed a challenge earlier. Direct systemic administration has led to several toxicities and side effects.

On the other hand, the challenge with mRNA was its rapid degradation in situ. But in modern times, mRNA is considered an ideal vehicle that is helping with cell targeting. Further, to prevent the rapid degradation of mRNA by ribonucleases, it can be encapsulated with suitable agents. This can thus increase its stability and improve its targeted delivery to cells.

What is in the pipeline for mRNA cancer treatment?

mRNA cancer vaccines can be used both in prophylaxis and treatment. After sequencing the target pathogen, designing the mRNA in way is needed to prompt the cells to produce target proteins. These proteins play an important role in producing the desired immune response.

Therefore, several mRNA cancer treatment companies are now testing various options.

  • BioNTech and Roche, in partnership, are conducting phase 1 trials of BNT122 for treating metastatic melanoma. This vaccine contains 20 different neoantigens.
  • Keytruda, an immunotherapy developed by Merck, is also being tested as an adjuvant therapy along with BioNTech’s BNT122 mRNA cancer vaccine.
  • Moderna’s personalized mRNA cancer vaccines, mRNA-4157 and mRNA-5671, can express tumour neoantigens to produce an immune response.

Conclusion

When the Covid-19 virus outbreak affected all corners of the globe, Comirnaty, the breakthrough mRNA-based Covid-19 vaccine developed by Pfizer & BioNTech, became a potent saviour. It is composed of a nucleoside-modified mRNA encoding the full-length spike protein of the mutated form of the SARS-CoV-2 virus. Encapsulated within lipid nanoparticles, the nucleoside-modified mRNA is administered via the IM route. So far the vaccine has shown promise in offering protection against Covid-19 in real-world conditions.

The mRNA cancer therapies and the Covid-19 vaccine work on the same principle: to produce an immune response against an antigen (cancer cells in case of the former and virus protein in case of the latter). However, mRNA cancer vaccines are therapeutic, while the Covid-19 vaccines offer protection against viral infections.

Growing incidences of mRNA’s clinical application, along with several preclinical and clinical studies, have already established that transcript-based anticancer therapies have strong potential and a bright prospect.

Read more about infections that can cause cancer.

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