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After Covid, mRNA vaccine for cancer? US researchers report initial success against melanoma

Mice treated with the mRNA vaccine, delivered like ones for Covid, showed reduction in tumours & long-term immune memory, says study by Tufts University researchers published in PNAS.

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New Delhi: Building on the experience of the ‘messenger RNA’ (mRNA) vaccine used against Covid, researchers at Tufts University in the US have reported success in animal models of an mRNA vaccine targeted against a type of melanoma.

A cancer of the cells that produce melanin, melanoma is widely regarded as the most serious variant of skin cancer.

In a paper published Monday in the peer-reviewed journal Proceedings of the National Academy of Sciences, the researchers described how they had delivered the mRNA in “tiny lipid bubbles”, or bubbles of ‘fat’, as is done in the Covid vaccines from Pfizer and Moderna.

In this case, instead being coded for the SARS-CoV-2 spike protein, the mRNA is coded for antigens found in cancer cells, and the lipid nanoparticles target the lymphatic system to “train” the immune cells against that particular kind of cancer, triggering a cancer immunotherapy pathway.

The lymphatic system is a network of tissues, vessels, and organs which move ‘lymph’, a clear fluid that helps fight infections and other diseases.

‘Immunotherapy’ refers to a mode of treatment in which the tumour cells are targeted by pumping up the patient’s own immune system to act more efficiently, instead of using extraneous chemicals and other agents.

“What we are doing now is developing the next generation of mRNA vaccines using lipid nanoparticle delivery technology with the ability to target specific organs and tissues,” said Qiaobing Xu, professor of biomedical engineering at Tufts and one of the authors of the study, in a statement issued by the university Monday .

“Targeting the lymphatic system helped us overcome many of the challenges that others have faced in developing a cancer vaccine,” he added.

Mice treated with this vaccine showed reduction in tumours, with about 40 per cent reporting “no tumours”. The latter group also reported no recurrence in the long-term when the vaccine was used in combination with existing therapies that can help prevent cancer cells suppressing an immune response.

Plus, none of the mice in complete remission developed any new tumours when injected with metastatic tumour cells, “showing that the cancer vaccine led to excellent immune memory”.


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Preventing liver damage

The Tufts researchers believe they may have found a way around the principal hurdle that remains in cancer mRNA vaccines — that of setting in motion a cycle of liver inflammation and damage because of unintended ‘expression’ of the antigens in the liver.

‘Gene expression’ is a process the cell uses to produce the molecule it needs by reading the genetic code written in the DNA or RNA.

“More than 20 mRNA cancer vaccines have been enrolled to date in clinical trials, but usually much of the mRNA ends up in the liver. While antigens produced in the liver can still induce an immune response, there remains a risk of liver inflammation and damage,” the statement said.

“The response could be more effective and long-lasting if more of the vaccine were directed to the lymphatic system, where B cells, T cells and other cells of the immune system are concentrated and learn to fight off unwelcome intruders,” it added.

The Tuft researchers made modifications in the lipid nanoparticle so that it settled in the mice’s lymph nodes instead of their livers.

“Cancer vaccines have always been a challenge because tumour antigens don’t always look so ‘foreign’, like antigens on viruses and bacteria, and the tumours can actively inhibit the immune response. This cancer vaccine evokes a much stronger response and is capable of carrying mRNA for both large and small antigens,” said Jinjin Chen, a postdoctoral research fellow at Tufts and part of Qiaobing Xu’s research team, in the statement.

“We are hoping that it could become a universal platform, not only for cancer vaccines, but also for more effective vaccines against viruses and other pathogens,” added Chen.

(Edited by Zinnia Ray Chaudhuri)


Also read: With ‘re-engineered T-cells’, US firm claims breakthrough in therapy for relapsed multiple myeloma


 

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