BioNTech, perhaps most famous nowadays from their effective mRNA vaccines in partnership with Pfizer to fight against COVID-19, had its eyes set on cancer treatments for a while now. Just as how mRNA-based developments provided them with their breakthrough against COVID-19, they may have just found the same success in cancer treatment using a similar methodology. Their results were published in the journal Science Translational Medicine.
Cytokines are small proteins that our bodies make that play a crucial role in regulating the growth and activity of other cells in the immune system and the blood. Cytokines are also known to boost anti-cancer activity within the body, as it sends signals to other parts of the body that help kill off abnormal cells and help our body’s normal cells live just that much longer, according to the American Cancer Society.
Applying cytokines into tumors in the body have been shown to decrease tumor sizes, leading to their eventual eradication. However, these proteins degrade quickly once within the body, as elevated levels of these can lead to toxicity in the body. As such, previous cancer treatments required constantly administering cytokines into a site in question, but with extreme caution and regulation, as elevated cytokine toxicity levels can hinder the progress of cancer treatment instead.
This led to the development of using viral vectors in order to deliver cytokines directly to a tumor; problem is, this form of treatment encountered interference from the patient’s immune system and also induced genetic issues, prompting reexamination and modification of the process to make it safer, as well as development of alternatives that can avoid the risks with using viral vectors entirely. Here, BioNTech attempted to address these issues by applying cytokines through mRNA therapy, in their treatment designated SAR441000 (BNT131).
The novel treatment involves inserting mRNA that code for cytokines directly into the tumor in question, in conjunction with other relevant therapies. The body then creates a large amount of localized cytokines that specifically target the tumor, fending off the growing mass of cancer cells until its eradication. BioNTech performed trials on 20 mice with melanomas, and found that 17 of them produced enough cytokines to effectively erase the mices’ melanomas within 40 days. Treatment of mice with two different tumors revealed that the cytokines traveled from the melanoma site towards the second tumor, inhibiting tumor growth on the second site as well. This, according to BioNTech, may imply their new treatment to be potent against solid tumors as well as any secondary tumors that may appear after eradicating the first. Unlike the previous treatments involving cytokines, treatment with their new mRNA methodology imparted no adverse effects on the mice, they added.
Since then, BioNTech has moved onto both Phase 1 and 2 of human trials, involving 231 participants. Preliminary data obtained from 17 participants last November 2020 revealed the participants experiencing no adverse side effects, showing promising results. BioNTech hopes further development of their new mRNA-based treatment can increase the scope of possible treatment sites beyond solid tumors like melanomas.
References
- American Cancer Society. (2019, December 27). Cytokines and Their Side Effects. American Cancer Society. Retrieved September 24, 2021, from https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/cytokines.html
- BioNTech. (n.d.). Pipeline. BioNTech. Retrieved September 24, 2021, from https://biontech.de/science/pipeline
- Klein, A. (2021, September 8). mRNA cancer therapy now in human trials after shrinking mouse tumours. New Scientist. Retrieved September 24, 2021, from https://www.newscientist.com/article/2289334-mrna-cancer-therapy-now-in-human-trials-after-shrinking-mouse-tumours/
- Hotz, C., Wagenaar, T. R., Gieseke, F., Bangari, D. S., Callahan, M., Cao, H., Diekmann, J., Diken, M., Grunwitz, C., Hebert, A., Hsu, K., Bernardo, M., Karikó, K., Kreiter, S., Kuhn, A. N., Levit, M., Malkova, N., Masciari, S., Pollard, J., … Wiederschain, D. (2021). Local delivery of mRNA-encoding cytokines promotes antitumor immunity and tumor eradication across multiple preclinical tumor models. Science Translational Medicine, 13(610), eabc7804. https://doi.org/10.1126/scitranslmed.abc7804
- Sanofi. (2021). A phase 1 first-in-human dose escalation and expansion study for the evaluation of safety, pharmacokinetics, pharmacodynamics and anti-tumor activity of sar441000 administered intratumorally as monotherapy and in combination with cemiplimab in patients with advanced solid tumors (Clinical Trial Registration No. NCT03871348). clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT03871348
