Cancer vaccines poised to unlock 'new treatment paradigm' with Merck/Moderna data

Gritstone bio

05/06/2023 13:00

By Julie Steenhuysen
       CHICAGO, June 5 (Reuters) - Adding an experimental
mRNA-based vaccine from Moderna Inc  MRNA.O  and Merck & Co
 MRK.N  reduced the risk that the most deadly skin cancer would
spread by 65% over treatment with an immunotherapy alone in a
midstage trial, the companies reported on Monday.
    The results, presented at the American Society of Clinical
Oncology meeting in Chicago, follow earlier promising data from
the trial showing the customized mRNA vaccine given in
combination with Merck's Keytruda cut the risk of death or
recurrence of melanoma by 44% compared with Keytruda alone.
    The findings add to a growing body of evidence suggesting
that mRNA technology, which rose to prominence during the
COVID-19 pandemic, can be used to assemble personalized vaccines
that train the immune system to attack the specific type of
cancer cells in a patient's tumors.
    Scientists have been chasing the dream of vaccines to treat
cancer for decades with few successes. Experts say mRNA
vaccines, which can be produced in as little as eight weeks,
paired with drugs that rev up the immune system may lead to a
new generation of cancer therapies.
    The hope is for "a completely new treatment paradigm in
cancer that will be better tolerated and unique to individual
patients' tumors," said Dr. Jane Healy, an executive overseeing 
in early cancer treatment development at Merck.
    The Merck/Moderna collaboration is one of several combining
powerful drugs that unleash the immune system to target cancers
with mRNA vaccine technology. Pfizer's  PFE.N  COVID vaccine
partner BioNTech SE  22UAy.DE  and Gritstone Bio Inc  GRTS.O 
are taking similar approaches using mRNA technology.
    The vaccines all target neoantigens, new mutations that are
only present on tumors. Aiming at these unique proteins allows
the immune system to kill cancer cells while leaving healthy
tissue unscathed.
    The trick is determining which of many mutations is driving
the cancer. 
    To accomplish this, tumors are removed and their genetic
makeup is mapped using next-generation DNA sequencing. Companies
use artificial intelligence to predict which mutations will be
the most effective targets. These are used to build an
individualized vaccine targeting only mutations in the patient's
tumor.
    During this process, patients typically receive an
immunotherapy such as Keytruda or Roche's  ROG.S  Tecentriq,
which block a mechanism cancer uses to hide from the immune
system.
    
    'A STARTING POINT'
    Long before COVID, companies had been eyeing messenger RNA
(mRNA) technology, which carries instructions for cells to make
specific proteins, as a vehicle for delivering a cancer vaccine.
    Merck and Moderna have been collaborating since 2016.   
Researchers at Memorial Sloan Kettering Cancer Center (MSK) in
New York began working with Germany's BioNTech in 2017.
    At that time, there was already proof that immunotherapy
could work in so-called "hot" tumors, or highly mutated cancers,
 such as melanoma. There was little hope it would work in "cold"
cancers with few mutations, such as pancreatic cancer, said
MSK's Dr. Vinod Balachandran.
    With standard treatment, 90% of pancreatic cancer patients
die within five years of diagnosis.
    Balachandran's team studied the rare long-term survivors and
found an immune system component called T cells in these
individuals were able to recognize mutations derived from the
cancer, raising the possibility of a targeted vaccine. 
    In a small ongoing trial testing a made-to-order BioNTech
vaccine plus Roche's Tecentriq, half of the 16 pancreatic cancer
patients mounted an immune response, and none showed signs of
relapse after 18 months, according to data published last month
in Nature. 
    Gritstone Bio is taking a different tack, combining two
types of customized vaccines in hopes of treating patients with
metastatic colon cancer, another cancer that has been largely
unresponsive to immunotherapy.
    The approach first primes the immune system with an older
technology called a chimpanzee adenovirus vaccine that targets
patients' tumors. That is followed by a personalized
self-amplifying mRNA vaccine, which includes an enzyme that
makes extra copies of the antigens, reducing the required dose.
    Gritstone is expecting data from a later-stage trial testing
its dual vaccine therapy in the first quarter of 2024.
    "Based on everything we've shown and we've published, we're
really excited," said Gritstone CEO Andrew Allen.
    Merck and Moderna are planning a larger Phase 3 trial in
melanoma and are also testing its combination in lung cancer.
    "We see this as a starting point," Healy said.

 (Reporting by Julie Steenhuysen
Editing by Caroline Humer and Bill Berkrot)
 ((julie.steenhuysen@thomsonreuters.com; 312-408-8131; Reuters
Messaging: Julie.steenhuysen.reuters.com@reuters.net))