Following the success of mRNA vaccines against the coronavirus, several biotech companies are using the technology to develop vaccines for a different "public health scourge": cancer, Jonathan Wosen writes for STAT.
With the "unprecedented success" of mRNA vaccines against the coronavirus, experts expressed hope that the technology could lead to the development of "new and better vaccines" against cancer, Wosen writes.
According to Wosen, "[t]he aim of any vaccine is to focus the immune system's response against a particular molecule, or antigen, whether that's a piece of a virus or a protein that coats tumor cells." However, cancer vaccines are primarily used as treatments, while the Covid-19 vaccine is used as a preventive measure.
"The tumor cells are already there. And you have to build an army of immune cells which is big enough," said Özlem Türeci, co-founder and CMO of BioNTech, which currently has eight different cancer vaccines undergoing clinical trials. "It's a numbers game to conquer a tumor, which means you have to be able to induce very strong immune responses."
Currently, biotech companies are developing two types of mRNA vaccines—"bespoke" vaccines that are tailored to a specific target, and "off-the-shelf" vaccines that target antigens shared across all patients, Wosen writes.
"The personalized approach starts by taking a sample of both a patient's cancer cells and healthy tissue," Wosen explains. "Researchers then compare the DNA and RNA sequences of these healthy and cancerous samples to identify mutations they can target with a vaccine."
Several biotech companies are currently pursuing this approach. For example, BioNTech in October 2021 launched a phase 2 trial for colon cancer patients who had remaining cancer cells in their blood after their tumors were surgically removed.
According to Wosen, the 200-person randomized study is currently evaluating whether the vaccine boosts the disease-free survival rate compared with the current standard practice, which only involves monitoring patients.
Moderna is also testing a personalized cancer vaccine strategy in phase 1 and phase 2 trials. Moderna's drug, called mRNA-4157, delivers mRNA coding for up to 34 tumor antigens, Wosen writes.
While the "bespoke" and "off-the-self" strategies both have pros and cons, the latter can be administered quickly to a wide range of patients, and the former "allows scientists to target a wider range of cancer antigens," Wosen writes. "And targeting multiple antigens decreases the odds that cancer cells will mutate in ways that make the vaccine useless, because the immune system will be attacking on multiple fronts," he adds. As a result, personalized vaccines may a better fit for fast-mutating cancers, Türeci noted.
However, experts currently have no way to determine whether a tailored or generic approach will work best, leading companies to test both approaches.
While BioNTech and Moderna both sequence a cancer cell's exome to identify potential vaccine targets, German biopharma company CureVac reads entire genomes instead—"driven by a growing recognition that the non-protein coding parts of the genome are far from 'junk' DNA," Wosen writes.
"Most of the differences between the cancer cell and the healthy cell when it comes to the antigens are encoded by what was then referred to as the junk DNA," said Ronald Plasterk, CureVac's SVP of innovation and science.
CureVac is also developing techniques to synthesize small amounts of mRNA to further its personalized vaccine work. CureVac in 2020 partnered with Tesla to develop small, portable mRNA "printers," Wosen writes
According to Plasterk, biotech companies face a series of challenges, including figuring out how to trigger immune responses that can affect tumors and finding the best way to combine cancer vaccines with current cancer treatments.
"There's a huge gap between what we know about cancer" and the current standard of care, he said. "I think immunotherapy will be a full fourth pillar in treatment of cancer in the years to come." (Wosen, STAT, 11/21)
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