The story so far: The results of a trial of an experimental cancer vaccine built on the mRNA (messenger ribonucleic acid) platform, made by Moderna and MSD (Merck&Co.), have shown promising results, media announcements claimed last week. Patients taking an immunotherapy drug Keytruda for advanced melanoma (a kind of skin cancer) were less likely to die or have the cancer recur, if they took the vaccine (mRNA-4157/V940) also, the companies said.
What did the trial involve?
It was a small study, involving 157 patients. The vaccine showed a 44% reduction in the risk of dying of cancer or having the cancer progress. Moderna’s Paul Burton was quoted as saying: “This is a significant finding. It’s the first randomised-trial testing of an mRNA therapeutic in cancer patients.” Reuters reported that “the combination was generally safe and demonstrated the benefit compared with Keytruda alone after a year of treatment. Serious drug-related side effects occurred in 14.4% of patients who received the combination compared with 10% with Keytruda alone.”
As a personalised cancer vaccine, it is tailor-made for every patient. As a consequence, it is expected to be very expensive to make. The results too will have to be independently scrutinised by experts, western media has reported. But oncologists across the world have welcomed this as an exciting new opportunity in cancer care.
How does the vaccine work?
The personalised cancer vaccine uses the same messenger-RNA technology that was used to produce the COVID vaccine. It allows the body’s immune system to seek and destroy cancerous cells, in this case melanoma, but with the hope that it could lead to new ways to fight other types of cancers too.
According to an article by Thomas Schlake et al, in RNA Biology, RNA as a therapeutic was first promoted in 1989 after the development of a broadly applicable in vitro transfection technique. A couple of years later, mRNA was advocated as a vaccine platform. He says, “mRNA offers strong safety advantages. As the minimal genetic construct, it harbours only the elements directly required for expression of the encoded protein.”
The refinement of the mRNA platform owes everything to COVID. Rapid advancements within a remarkable period of one year allowed the technology to gain several revolutionary steps ahead, in order for it to be used successfully to drive vaccines that work. While the mRNA vaccines were notoriously unstable, in the National Cancer Institute website on ‘Can mRNA Vaccines Help Treat Cancer?’ Edward Winstead writes that researchers have learned how to engineer stable forms of mRNA and deliver these molecules to the body through vaccines. “Once in the body, the mRNA instructs cells that take up the vaccine to produce proteins that may stimulate an immune response against these same proteins when they are present in intact viruses or tumour cells.” The mRNA-based cancer treatment vaccines have reportedly been tested in small trials for nearly a decade, with some promising early results.
As far as the SARS-CoV-2 vaccine was concerned, the mRNA included in the Pfizer-BioNTech and the Moderna vaccines instructs cells to produce a version of the “spike” protein that studs the surface of SARS-CoV-2, he explains. The immune system sees this spike protein as foreign and mobilises immune cells to produce antibodies to fight off the infection.
A Reuters story on the breakthrough study explained that the personalised cancer vaccine works in concert with Merck’s Keytruda, to disable a protein called programmed death 1, or PD-1, that helps tumours to evade the immune system. To build the vaccine, researchers took samples of patients’ tumours and healthy tissue. After analysing the samples to decode their genetic sequence and isolate mutant proteins associated only with the cancer, that information was used to design a tailor-made cancer vaccine. When injected into a patient, the patient’s cells act as a manufacturing plant, producing perfect copies of the mutations for the immune system to recognise and destroy. Having been exposed to the mutations without the virus, the body learns to fight off the infection.
What does it mean for the future?
Vincent Rajkumar, Editor-in-Chief, Blood Cancer Journal, and Professor, Mayo Clinic, told The Hindu, “It’s a really important result and shows the potential of mRNA vaccine technology.”
Listing out CAR-T cells and bi specific antibodies among newer cancer therapies, he said both approaches have already produced spectacular results in many cancers.While in CAR-T treatment, scientists take the immune systems cells out, engineer them to target a specific cancer and then put them back in the body to kill cancer cells, bispecific antibodies attach to immune system cells with one arm and cancer cells with the other, thereby bringing powerful immune system killer cells right next to the cancer cells. A few bispecific antibodies have been FDA-approved already, he said.
“The possibility of using mRNA vaccine technology to fight cancer just got a boost. The idea of cancer vaccines has been around for a long time. But mRNA vaccine technology and personalisation of the vaccine that it allows provides a lot of optimism,” Dr. Vincent explained. On a more general note, he added, technology has managed to connect investigators like never before, making collaborations between nations much easier.
