By May of this year another threat to personalized mRNA vaccines for cancer was coming into focus:

🔥mounting federal hostility to vaccines.

Senate Republicans convened a hearing entitled

“The Corruption of Science and Federal Health Agencies,”

featuring the false claim that as many as three out of four deaths from COVID were caused by mRNA vaccines deployed to stop the pandemic.

(In fact, COVID vaccinations saved an estimated 2.5 million lives between 2020 and 2024,
according to a study published earlier this year.)

In June, Kennedy fired all 17 members of the Advisory Committee on Immunization Practices,
which makes recommendations on federal vaccine policy.

He eventually replaced them with his own advisory committee,
which includes several anti-vaccine stalwarts.

Kennedy has also slashed research funding for mRNA vaccines.

In August he canceled nearly $500 million supporting the development of mRNA vaccines against viruses such as SARS-CoV-2 and influenza.

The move intensified the fears of researchers who want to develop mRNA vaccines for other illnesses,
among them cancer.

After my visit to Memorial Sloan Kettering, Balachandran’s team shared a chart that plotted Brigham’s immune response to her personalized mRNA vaccine.

Along the bottom, triangles marked the dates of her surgery
and each of the nine doses of the vaccine she received over the course of a year.

Above them a cluster of brightly colored lines showed the share of her body’s
T cells targeting the specific mutant proteins in her cancerous tumor.

At first, when Brigham’s tumor was removed,
cells trained to go after each cancer clone were somewhere on the order of one in 500,000 T cells in her blood.

A few months after surgery,
when she’d had four doses of the vaccine,
the lines shot up almost vertically, showing that the most common cancer fighter at that point accounted for around one in 20 to one in 50 T cells
—an increase of more than 20,000-fold.

Those T cells dipped a bit in the months before Brigham’s last booster shot,
given almost a year after her tumor was removed.

But they remained in the same range even three years on.

A phase 2 clinical trial evaluating the safety and efficacy of the vaccine in a larger patient group is currently underway.

The vaccine for Brigham’s cancer was just nine tiny vials of liquid administered through an IV,
a private message that only her immune system was meant to decode.

But the effort that delivered that coded message was a deeply collective enterprise,
one that stretches back through the hundreds of thousands of tissue samples collected,
stored and analyzed at Memorial Sloan Kettering,
-- each one taken from the body of a patient who might not have survived their cancer.

Also in that vaccine were the contributions of generations of taxpayers who never got to see these results.

Perhaps their descendants will be able to beat the disease
—if society continues to support this vital work.

https://www.scientificamerican.com/article/personalized-mrna-vaccines-will-revolutionize-cancer-treatment-if-federal/

#micrometastases #neoantigens #driverantigens
#passengermutations #neoantigens #checkpointinhibitors #WilliamColey #immunotherapy #stroma #MHC

By May of this year another threat to personalized mRNA vaccines for cancer was coming into focus:

🔥mounting federal hostility to vaccines.

Senate Republicans convened a hearing entitled

“The Corruption of Science and Federal Health Agencies,”

featuring the false claim that as many as three out of four deaths from COVID were caused by mRNA vaccines deployed to stop the pandemic.

(In fact, COVID vaccinations saved an estimated 2.5 million lives between 2020 and 2024,
according to a study published earlier this year.)

In June, Kennedy fired all 17 members of the Advisory Committee on Immunization Practices,
which makes recommendations on federal vaccine policy.

He eventually replaced them with his own advisory committee,
which includes several anti-vaccine stalwarts.

Kennedy has also slashed research funding for mRNA vaccines.

In August he canceled nearly $500 million supporting the development of mRNA vaccines against viruses such as SARS-CoV-2 and influenza.

The move intensified the fears of researchers who want to develop mRNA vaccines for other illnesses,
among them cancer.

After my visit to Memorial Sloan Kettering, Balachandran’s team shared a chart that plotted Brigham’s immune response to her personalized mRNA vaccine.

Along the bottom, triangles marked the dates of her surgery
and each of the nine doses of the vaccine she received over the course of a year.

Above them a cluster of brightly colored lines showed the share of her body’s
T cells targeting the specific mutant proteins in her cancerous tumor.

At first, when Brigham’s tumor was removed,
cells trained to go after each cancer clone were somewhere on the order of one in 500,000 T cells in her blood.

A few months after surgery,
when she’d had four doses of the vaccine,
the lines shot up almost vertically, showing that the most common cancer fighter at that point accounted for around one in 20 to one in 50 T cells
—an increase of more than 20,000-fold.

Those T cells dipped a bit in the months before Brigham’s last booster shot,
given almost a year after her tumor was removed.

But they remained in the same range even three years on.

A phase 2 clinical trial evaluating the safety and efficacy of the vaccine in a larger patient group is currently underway.

The vaccine for Brigham’s cancer was just nine tiny vials of liquid administered through an IV,
a private message that only her immune system was meant to decode.

But the effort that delivered that coded message was a deeply collective enterprise,
one that stretches back through the hundreds of thousands of tissue samples collected,
stored and analyzed at Memorial Sloan Kettering,
-- each one taken from the body of a patient who might not have survived their cancer.

Also in that vaccine were the contributions of generations of taxpayers who never got to see these results.

Perhaps their descendants will be able to beat the disease
—if society continues to support this vital work.

https://www.scientificamerican.com/article/personalized-mrna-vaccines-will-revolutionize-cancer-treatment-if-federal/

#micrometastases #neoantigens #driverantigens
#passengermutations #neoantigens #checkpointinhibitors #WilliamColey #immunotherapy #stroma #MHC

At both Moderna and BioNTech, the complex logistics of conducting the dozens of different quality-control tests required for each production run falls to algorithms powered by AI.

Before being approved for release, doses of SpikeVax underwent 40 distinct tests that tracked the chemistry, biochemistry, microbiology and sterility of every vial.

With COVID vaccines, the sterility test alone,
which ensures that vials are not contaminated with organisms,
took two weeks.

Refinements have since compressed that test to eight days, Nickerson says.

Ultimately the goal is to shrink it to five days and complete the other tests within that same window.

“The reason it’s hard is we have to design the equipment,”
he explains.

“None of this stuff’s off-the-shelf.”

At the same time, the background science is,
at least in theory,
easily adapted from work that’s already been done.

Lennard Lee,
an adviser to the U.K.’s National Health Service overseeing the rollout of clinical trials for cancer vaccines,
says the pandemic gave regulators there a running start on trials for mRNA cancer vaccines.

In partnership with BioNTech, the NHS launched a program that aims to provide personalized vaccines to up to 10,000 cancer patients in the next five years.

And the NHS and Moderna have invested in a facility that could produce up to 250 million vaccines per year.

In that interval,
as manufacturers work to reduce production times and costs,
clinical trials will evaluate alternative dosage and delivery mechanisms, Lee says.

Although current protocol is for vaccines to target #micrometastases
—small groups of cancer cells that spread to other parts of the body
and linger after cancerous tumors are removed surgically
—there’s no shortage of adjustments that might follow from more data
or improved screening.

Could one deliver a therapeutic vaccine to tackle a tumor before it is large enough to operate on?

Or maybe one could even administer a prophylactic shot that prevents tumor formation in the first place?

With a unified health system and world-class research and manufacturing facilities, Lee says,
the U.K. is well positioned to advance research that would answer such questions.

Fully realizing the potential of personalized mRNA vaccines for cancer, however,
will require more trials in the U.S.,
which has many more cancer research centers than the U.K.

⚠️But the ability of the U.S. to lead this effort is now in jeopardy.

The federal government has long been the dominant source of funding for cancer research in the U.S.

Miriam Merad, a cancer immunologist at the Icahn School of Medicine at Mount Sinai in New York City, says that
in a typical year, funding from the NIH accounts for more than half of the research budget at her institution.

In President Donald Trump’s first term, threatened cuts to the NIH never quite materialized.

Society is not going to let that happen,
Merad thought.

🆘 But just weeks into Trump’s second term, the NIH announced plans to limit indirect contributions to research grants to 15 percent,
-- meaning that for every $100 in funding awarded, only $15 extra would be included for overhead
—a dramatic departure from historical rates in the range of 50 to 60 percent.

“This is an operation,” Merad says,
gesturing to the building where she works,
which is dotted with six-figure pieces of equipment
and has an entire floor dedicated to rearing mice used in research.

“We have to pay salaries;
we have to buy food for the animals.
We have to pay service contracts because we have instruments that need to be serviced all the time.”

These are not expenses that can be easily paused or restarted
based on the fate of a single grant.

Within just a few months of the NIH announcement,
Merad’s department had reduced hires of new postdocs,
and Mount Sinai’s medical school had to shrink the size of its incoming class.

#neoantigens #driver #antigens #passenger #mutations #neoantigens #checkpointinhibitors #WilliamColey #immunotherapy #stroma #MHC