- Health
Modified RNA in COVID-19 vaccines isn’t linked to cancer development
Key takeaway
The mRNA COVID-19 vaccines contain RNAs with chemical modifications that increase their stability and improve their ability to induce a potent immune response. Some results suggest that such chemical modifications make mRNA-based anti-cancer vaccines less effective. However, it doesn’t mean that COVID-19 vaccines increase the risk of cancer. There’s no evidence that COVID-19 vaccination increases the risk of cancer.
Reviewed content
Verdict:
Claim:
A review “has found that COVID-19 mRNA vaccines could aid cancer development”
Verdict detail
Misrepresents source: The claim originates from the conclusion of a literature review based on a study by Sittplangkoon and colleagues. However, this review didn’t accurately represent the study’s findings. Contrary to the claim, the study didn’t show that modified mRNA like those used in COVID-19 vaccines enhanced cancer development.
Inadequate support: The claim suggested that new results established a link between COVID-19 vaccines and cancer development. However, the scientific publication used to support that claim is a literature review. This form of publication summarizes existing knowledge but doesn't provide any new results.
Full Claim
A review “has found that COVID-19 mRNA vaccines could aid cancer development”; “Confirmed: Researchers Reveal COVID mRNA Vaccines Contain Component that Suppresses Immune Response and Stimulates Cancer growth”; “not only could the COVID-19 mRNA jabs aid cancer development, but they could actually cause and worsen cancer, not make it better”
Review
Science Feedback and other organizations have repeatedly refuted unsupported claims and flawed public health data analyses suggesting that the COVID-19 vaccines increase the risk of cancer. We also explained that a predicted increase of new cancer diagnoses in the U.S. in 2024 was unrelated to COVID-19 vaccination and could plausibly be explained by population aging and delayed cancer screening and treatment during the pandemic.
However, the organization America’s Frontline Doctors, known for spreading COVID-19 disinformation, continues to push this narrative. More recently, it claimed that an April 2024 scientific publication by Rubio-Casillas et al. “found that COVID-19 mRNA vaccines could aid cancer development”[1].
The website The HighWire, which has previously published false claims about COVID-19 and vaccines, also wrote that the scientific paper showed that “mRNA vaccines could aid cancer development”. The HighWire cited Peter McCullough, a cardiologist known for spreading misinformation about COVID-19 vaccines. McCullough said that “not only could the COVID-19 mRNA jabs aid cancer development, but they could actually cause and worsen cancer, not make it better”.
However, this claim is unsubstantiated. The scientific publication presented as evidence for this claim doesn’t contain new results that support the claim and it misinterprets results from another study.
The paper by Rubio-Casillas et al. didn’t find anything new
To begin with, this paper by Rubio-Casillas et al. isn’t a study. It doesn’t contain new experimental or clinical results. Instead, the authors conducted a review of already-existing literature.
This is a crucial difference between studies and literature reviews. A study formulates a hypothesis and tests it by conducting experiments, data analysis, and trials, thereby producing new knowledge.
By contrast, a literature review summarizes what is already known and provides a critical analysis of results and competing hypotheses. This can lead to formulating new hypotheses and identifying new avenues of research, but it doesn’t in itself demonstrate anything new. New hypotheses that may arise still would need to be confirmed experimentally and clinically. Thus, the claim that this paper “has found” a link between COVID-19 vaccines and cancer isn’t correct, because it didn’t test that hypothesis with experiments and clinical trials.
Rubio-Casillas et al. misinterpreted key study underpinning their claim
The main claim of Rubio-Casillas et al. was that the mRNA used in COVID-19 mRNA vaccines contained chemical modifications that allegedly “stimulated cancer growth and metastasis”, thus “suggesting that COVID-19 mRNA vaccines could aid cancer development”.
This refers to modified nucleotides—the building blocks of RNAs and DNAs—used in the COVID-19 mRNA vaccines. More specifically, instead of the nucleotide uridine, the vaccine mRNA contains N1-methyl-pseudouridine.
Unmodified RNAs—using normal uridine—trigger an inflammatory response and are rapidly degraded upon entering a cell. By contrast, modified RNAs using N1-methyl-pseudouridine are able to evade the cell’s RNA detection system and don’t trigger inflammation[2]. Vaccines using modified RNA are able to induce greater antigen production, are better tolerated due to a lower inflammation, and induce a stronger immune memory[2]. It was the discovery of modified RNA’s immunomodulating potential that won Katalin Karikó and Drew Weissman the Nobel Prize in Physiology or Medicine in 2023.
Rubio-Casillas et al. heavily relied on a study by Sittplangkoon et al. to support their claim that N1-methyl-pseudouridine, although useful for vaccine effectiveness, could also favor the development of cancer[3]. Indeed, Sittplangkoon et al. is the only study cited in the review that directly investigates the effect of uridine modifications in cancer immunity.
Furthermore, Rubio-Casillas et al. claimed in their abstract that “evidence is provided[…] suggesting that COVID-19 mRNA vaccines could aid cancer development”. This sentence refers to the work by Sittplangkoon et al. and has been repeated in several versions of the claim.
However, this is an incorrect interpretation of this study, as we explain below.
It’s important to clarify that Sittplangkoon et al. didn’t investigate whether COVID-19 vaccines enhance cancer development. In fact, their work focused on anti-cancer vaccines, that is, a vaccine boosting immunity against a specific cancer, the same way that COVID-19 vaccines boosts immunity against the SARS-CoV-2 virus.
To do this, the researchers injected mice with melanoma cells (melanoma is a type of skin cancer) producing the protein ovalbumin (a protein abundant in egg whites). At the same time, they immunized the mice with a vaccine containing mRNA containing the genetic information to produce that ovalbumin protein. The objective was to train the mice’s immune systems to recognize and destroy ovalbumin-carrying melanoma tumors, just like the COVID-19 vaccine trains the immune system to recognize and destroy the spike-carrying SARS-CoV-2.
From the start, we can see that Sittplangkoon and colleagues were addressing a completely different scientific question from the one that Rubio-Casillas et al. tried to address. Rubio-Casillas et al. debated whether COVID-19 mRNA vaccines, which contain mRNA for the spike protein to build immunity against a virus, could inadvertently impair our immune defense against naturally-occurring cancers. By contrast, Sittplangkoon et al. asked whether modified and unmodified RNAs could be used in a vaccine targeting a specific, artificially-induced cancer.
Sittplangkoon et al. found that the anti-cancer vaccines that used unmodified RNAs efficiently boosted immunity against the melanoma. By contrast, the vaccines using modified RNAs didn’t improve immunity against melanoma compared to unvaccinated, healthy mice (Figure 1).
Figure 1 – Effect of anti-cancer vaccines containing either modified or unmodified RNAs on tumor growth. This graph represents melanoma growth in mice that are unvaccinated, or vaccinated with modified or unmodified mRNA. Modified RNA containing N1-methyl-pseudouridine is indicated by “100% m1Ψ”. Grey line: Mice vaccinated with unmodified RNA. Blue line: mice vaccinated with modified mRNAs. Red, orange and green lines: mice that haven’t been vaccinated. Source: Sittplangkoon et al[3].
It’s important to emphasize that mice vaccinated with modified RNAs didn’t fare worse than unvaccinated mice. So, the presence of N1-methyl-pseudouridine didn’t hamper the mice’s immunity against cancer; it just didn’t improve anti-cancer immunity.
In summary, the results of Sittplangkoon et al. suggest that anti-cancer vaccines would be more effective if they didn’t contain modified RNAs. But they didn’t show that the N1-methyl-pseudouridine contained in modified mRNA was detrimental to anti-cancer immunity of our body. In the absence of such a finding, the claim by Rubio-Casillas et al. is unsubstantiated and misrepresents the original study by Sittplangkoon et al. We reached out to Rubio-Casillas et al. to know if they had considered the results from Sittplangkoon et al. that we presented here.
The first author, Alberto Rubio-Casillas, replied via email, acknowledging that their publication “is a review article, not an experimental work” and it had been “distorted on social networks”. The authors stood by their conclusions, but didn’t provide new evidence to refute our conclusion that mice immunized with modified RNA had an equivalent or better outcome than non-immunized mice.
In conclusion, Rubio-Casillas et al. offered no new data to support the claim that COVID-19 vaccines cause cancer or favor cancer development. This claim strongly relies on a study by Sittplangkoon et al. that was unrelated to COVID-19 vaccines and didn’t show what Rubio-Casillas et al. claimed it did.
UPDATE (6 May 2024):
We updated our review with comments by Alberto Rubio-Casillas, the first author of the review. This information can be found in the twenty-first paragraph.
REFERENCES
- 1 – Rubio-Casillas et al. (2024) Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer? International Journal of Biological Macromolecules.
- 2 – Morais et al. (2021) The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines. Frontiers in Cell and Developmental Biology.
- 3 – Sittplangkoon et al. (2022) mRNA vaccine with unmodified uridine induces robust type I interferon-dependent anti-tumor immunity in a melanoma model. Frontiers in Immunology.
