New Developments in mRNA Cancer Vaccines
In August, Merck along with Moderna announced that their mRNA cancer vaccine, known as intismeran autogene, showed promise in slowing the recurrence and spread of melanoma when added to existing treatments. This was a highly anticipated news in the medical community, and Karen Knudsen, CEO of the Parker Institute—a research organization started by Sean Parker—expressed that the results indicated that using messenger RNA to educate the immune system against cancer cells, a concept that’s been around for quite some time, is now gaining traction for future drug initiatives.
However, just a few days later, BioNTech, a German pharmaceutical company, and its partner Genentech decided to halt a mid-stage study for their colorectal cancer vaccine. Their analysis of preliminary data revealed that the treatment wasn’t effective.
As researchers await more detailed findings from Moderna and Merck that are set to be shared at an upcoming European oncology meeting next month, there are already some questions bubbling up regarding these contrasting results.
Jason Luke, a physician and investigator who recently joined Strand Therapeutics, raised an important point: Why is it that Moderna’s data on melanoma appears positive, while BioNTech’s results on colorectal cancer do not? It’s a perplexing situation.
When BioNTech announced the discontinuation of its trial, analysts, including Cowen’s Yaron Werber, suggested that part of the answer might lie in the choice of colorectal cancer as a target. This type of cancer is often described as a “cold” tumor—meaning that it tends to be more challenging for immune cells to infiltrate. In contrast, melanoma is generally regarded as more conducive to immune cell activity.
Personalized cancer vaccines like intismeran and the autogene cevumeran from BioNTech and Genentech are crafted to stimulate the immune system. They use mRNA to generate specific mutated proteins from a patient’s tumor that serve as antigens, essentially acting like notices to the immune system. Yet, even with the vaccine potentially signaling the presence of colorectal cancer, that tumor might still resist immune attacks.
This theory seems reasonable, but it’s premature to reach definitive conclusions, as Georgina Long, an oncologist and medical director at the Melanoma Institute Australia, pointed out.
Long has collaborated with both BioNTech and Moderna on cancer vaccines and is working with Strand on mRNA-based treatments that enhance immune cell response against cancer. She mentioned that intismeran might actually be effective for patients with “colder” tumors. In their Phase 2 trial, Merck and Moderna gathered extensive data, including insights on how patients with different immune system markers responded. While melanoma is mostly seen as a “hot” tumor, individual cases can show a stark range of immune activity, and some patients do experience lower immune responses.
An interesting bit of data from their findings suggested that patients with lower levels of the immune marker PD-L1 appeared to gain more from the addition of intismeran to their treatment.
Researchers noted that comparing the results of intismeran and autogene cevumeran trials is complicated. For instance, intismeran was used alongside Keytruda, a drug that helps immune cells overcome obstacles set up by cancer cells and has been effective for many cancer types. On the other hand, autogene cevumeran was given on its own. This discrepancy in trial structure might account for the differing outcomes, perhaps suggesting that the current lineup of drugs doesn’t function as well in isolation.
BioNTech is now looking into whether combining autogene cevumeran with other treatments will be beneficial for patients suffering from pancreatic ductal adenocarcinoma, another type of “cold” tumor. The company clarified that the stoppage of the colorectal cancer trial won’t affect the ongoing pancreatic cancer trial, which is expected to conclude in 2031.
Strand Therapeutics is also exploring responses of various cancers to mRNA treatments independently, including cases where traditional drugs like Keytruda have failed.
Strand’s strategy stands apart from that of conventional cancer vaccine developers by utilizing mRNA to promote the production of an immune protein called interleukin-12, differing from the traditional vaccine model that targets specific tumor antigens.
According to Luke from Strand, the most straightforward path in developing this new generation of mRNA cancer therapies is to build on the successes seen with immunotherapy drugs like Keytruda.
The Boston-based startup has yielded encouraging results in melanoma and is now initiating early-stage trials in patients with non-small cell lung cancer, among other types.
Moreover, there have been positive early-stage results for therapies targeting challenging “cold” cancers like glioblastoma and pancreatic cancer. The Parker Institute is also teaming up with Medici Therapeutics, which has plans for a trial on Merkel cell carcinoma.
