Mastodawn

When the immune system detects a protein from a pathogen,
it’s supposed to dispatch killer T cells to eliminate the invader.

Some cancers can interfere with this process by hijacking the checkpoint proteins that keep our immune system from revving out of control
and using them to turn T cells off.

Starting in the mid-1990s, several research teams found success by treating mice with #checkpoint #inhibitors,
-- then a new class of drugs designed to keep tumor cells from concealing their identity and signaling, effectively, “nothing to see here.”

Thirty years on, checkpoint inhibitors have become a transformative tool in cancer treatment, especially for melanoma.

The research that went into developing checkpoint inhibitors showed conclusively that immune cells detect cancer much in the same way they identify other pathogens:

through differences in protein structure determined by DNA
—a crucial insight.

But as revolutionary as checkpoint inhibitors have been for immunotherapy, they don’t work for everyone
—far from it.

Some 80 percent of patients do not respond to this class of drugs.

Researchers are still trying to understand all the mechanisms that play a role in determining who does respond,
but one key factor is whether the immune system is able to recognize tumor cells on the basis of their mutations.

This is where mRNA vaccines come in.

#Jason #Luke, a melanoma researcher who now serves as chief medical officer of mRNA-medicine start-up #Strand #Therapeutics,
helped to design several ongoing clinical trials of mRNA vaccines for cancer.

He explains that both checkpoint inhibitors and mRNA vaccines build on our deep evolutionary adaptation for fighting pathogens
by identifying the proteins they shed in our bodies.

But checkpoint inhibitors are effective only if the patient’s immune system recognizes the cancer as a threat.

In contrast, mRNA vaccines have the potential to work even in patients whose cancers haven’t spurred much immune response.

The trick, Luke says, is using computational tools to decipher which of a given tumor’s mutations are most likely to be found by the immune system.

#MichaelMemoli
#WilliamColey #immunotherapy #stroma #MHC

Chuck Darwin Jan 17

Vaccines based on mRNA can be tailored to target a cancer patient’s unique tumor mutations.

But crumbling support for cancer and mRNA vaccine research has endangered this promising therapy

The results of Brigham’s trial were an early sign that mRNA vaccines may be effective for a wide variety of cancers:

Whereas pancreatic cancer is known for its low rate of mutations,
the earliest data on personalized mRNA vaccines came from studies of melanoma,
which researchers had targeted specifically because it tends to mutate so frequently.

An earlier phase 2 trial in patients with advanced melanoma found that for those who received both a personalized mRNA vaccine and so-called immune checkpoint inhibitors,
the risk of death or recurrence decreased by almost half compared with those who got only checkpoint inhibitors.

Ongoing companion trials are targeting kidney and bladder carcinomas
and lung cancer.

. In each case, the vaccine is additive:

administered after surgery and with standard drugs.

The shot’s job is to prime the immune system to recognize abnormal proteins arising from mutations
and attack any lingering malignancy that escaped conventional treatments
—or stamp out future recurrence.

Seeing promising results in fundamentally different kinds of tumors has motivated researchers to pursue personalized mRNA vaccines much more broadly.

In doing so, they’ve developed an approach at the nexus of several important trends,
pairing insights about our immune system’s response
to cancer
with advances in vaccine production spurred by the COVID pandemic,
the rise of algorithms powered by artificial intelligence,
and the plummeting cost of genetic sequencing.

Today there are at least 50 active clinical trials in the U.S., Europe and Asia
targeting more than 20 types of cancer.

A melanoma trial led by pharmaceutical companies Moderna and Merck has now reached phase 3,
the last step before a medicine can be approved for public consumption.

Personalized melanoma vaccines could be available as early as 2028,
with mRNA vaccines for other cancers to follow.

But the promise of this novel approach couldn’t have come at a more perilous time for the field.

🆘 In the first weeks of the second Trump administration,
U.S. cancer research was thrown into unprecedented turmoil as federal grants were terminated en masse.

According to one Senate analysis, funding from the National Cancer Institute was cut by 31 percent in just the first three months of 2025.

By March cancer researchers worried that mRNA vaccines were facing particular scrutiny.

⚠️KFF Health News reported that
#MichaelMemoli ,
acting director of the National Institutes of Health,
had asked that any grants, contracts or collaborations involving mRNA be flagged for Health and Human Services Secretary Robert F. Kennedy, Jr., best known prior to assuming that role as one of the nation’s most prominent anti-vaccine campaigners.

🔥Suddenly, the optimism around personalized mRNA vaccines was overshadowed by a sense that the public investment that sustained cancer research was being dismantled piece by piece.
https://www.scientificamerican.com/article/personalized-mrna-vaccines-will-revolutionize-cancer-treatment-if-federal/

Personalized mRNA Vaccines Will Revolutionize Cancer Treatment—If Federal Funding Cuts Don’t Doom Them

Vaccines based on mRNA can be tailored to target a cancer patient’s unique tumor mutations. But crumbling support for cancer and mRNA vaccine research has endangered this promising therapy

Scientific American