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Big News: Moderna and Merck Report Phase 2b Data for an mRNA Cancer Vaccine + Pembrolizumab
Further Evidence that the Central Hypothesis is gaining traction in cancer immunotherapy
This morning the news broke that the KEYNOTE 942 Phase 2b clinical trial of a novel combination therapy for advanced melanoma yielded a significant survival advantage for patients. Moderna and Merck reported on results generated by treating patients with a combination of a customized multi-epitope mRNA vaccine and pembrolizumab.
Why is this data important?
For decades, scientists have known that the ability to “vaccinate” against an individual patient’s tumor cells would likely lead to important clinical advantages. Previous approaches utilized protein or peptide neo-antigens prepared in a customized fashion from tumor tissue taken from each patient during surgery or biopsy. However, preparation of cancer vaccines using such technology was slow, expensive, frustratingly irreproducible, and only yielded a few objective clinical responses.
Might there be a better, faster, and more efficient way to prepare individual patient cancer vaccines? Enter mRNA technology and Moderna.
Instead of laborious protein or peptide neo-antigen isolation and preparation procedures, mRNA allows for the in situ production of tumor neo-antigens. These neo-antigens then prime the patient’s immune system to generate an attack specifically against the tumor. Moreover, mRNA technology turbocharges the process of selecting the best mix of neo-antigens for a patient, and packaging the chosen mRNA sequences into a carefully engineered delivery vehicle.
Some readers are now thinking, “Hmmm, Moderna - Aren’t they the company that went from a standing start in Jan-2020 to an approved COVID vaccine in Dec-2020? Well, yes…that was indeed Moderna.
The very same technology that powered Moderna’s SpikeVax(R) COVID vaccines lies at the heart of its cancer vaccines. This is a classic example of how investment in basic technology development often reaches critical mass, and then becomes very useful in multiple applications. It can take over a decade (or decades) to become an overnight sensation.
A lot of work still remains, including a Phase 3 clinical trial, and scaling of the cGMP manufacturing processes to efficiently take in a patient’s tumor biopsy tissue and transform it into a customized mRNA cancer vaccine. But we should be confident that this will happen. Two motivated and well-capitalized companies are focused on getting results that matter.
How can today’s clinical results in melanoma potentially be leveraged to benefit brain cancer patients?
If you have been regularly reading the posts at MissionGBM, you may recall that we are advocates of the Central Hypothesis of cancer immunotherapy:
For the most effective immunotherapy, transform the tumor micro-environment (TME) from immunologically “cold” to “hot” by applying a “Perturbation”. There are multiple ways to heat up a tumor, and today’s results indicate that well-designed cancer vaccines can be an attractive Perturbation.
Introduce a targeted immunotherapy to attract and sustain cytotoxic T-lymphocyte (CTL) activity in the TME. Pembrolizumab plays this role in the Moderna/Merck trial.
If possible, add a therapeutic agent that reverses the immuno-suppression caused by MDSCs in the TME.
For Julie’s customized GBM treatment protocol, we invoked the Central Hypothesis in Feb-2022 by using:
Tumor Treating Fields as the Perturbation
Pembrolizumab to attract and sustain CTLs to the TME
We chose this approach because the peptide-based tumor vaccines available at the time under experimental protocols were either too slow to be manufactured, or frankly, did not have compelling pre-clinical and clinical data sets.
Awesome work performed by all of the dedicated scientists and clinicians at Moderna and Merck over many years!
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