The success of mRNA-based COVID-19 vaccines has significantly boosted confidence in the design and building of mRNA-based therapeutic cancer vaccines. Two such vaccines are taking place: mRNA vaccine against pancreatic cancer and mRNA vaccine against advanced melanoma.
Recap on mRNA vaccine and host immune response
Using the replacement pseudouridine which provides stability with reduced adverse immune response, mRNA is designed, synthesized, and packaged in lipid nanoparticles. Upon injection, the mRNA gets internalized by dendritic cells (DC), a major antigen processing and antigen presentation immune cell type. DC makes the cancer neoantigen protein based on the mRNA instruction and displays the neoantigen on major histocompatibility complex (MHC) class I, or MHC-I. The T cell receptor (TCR) on cytotoxic T cells (CTL) recognizes the neoantigen, becomes activated, ready to recognize cancer cells that harbor the same neoantigen. Upon interacting with cancer cells, CTL unleashes its elimination machinery that activates the apoptotic pathway, leading to cancer cell destruction.
Pancreatic Cancer
The mRNA vaccine against pancreatic cancer is the fruition of a scientific collaboration by Memorial Sloan Kettering Cancer Center (MSKCC) and BioNTech, a biotech company headquartered in Mainz, Germany. The experimental process started in 2021 during the height of the COVID-19 pandemic. Undeterred, the scientists in the United States and Germany carried out the work as follows, summarized into sequential steps:18
- Step 1: A group of 16 pancreatic patients were recruited for the study.
- Step 2: Experienced surgeons at MSKCC performed intricately carried out surgical removal of the patient’s tumor and shipped it to BioNTech in Germany.
- Step 3A: While waiting for the vaccines to be designated and manufactured at BioNTech, oncology physicians at MSKCC administered an immune checkpoint inhibitor drug called PD-1 to all 16 patients.
- Step 3B: At BioNTech, scientists extracted genomic DNA from each patient’s tumor sample and subjected tumor genome sequencing followed by sequence analysis to select neoantigen proteins uniquely specific to the patient. Of a very important note, a cluster of 20 neoantigens was selected for each patient for the tailor-designed pancreatic vaccine for all 16 cancer patients.
- Step 4: The prepared vaccines were shipped back to MSKCC, where oncology physicians infused the vaccine to each patient in a 9-week regimen.
- Step 5: Upon completion of vaccine infusion, all patients were monitored closely for one and a half years.
The first encouraging observation is that all patients who have received the vaccine were free of tumor relapse for 18 months, which was a great step since typically after surgery, pancreatic patients see their tumor return around 13 months post-surgery. It is important to keep in mind that all 16 patients received PD-1, the potent immune checkpoint inhibitor before receiving the mRNA vaccine. Thus, the observed results could have been due to the effect of the drug or even a combination of drug + vaccine.
Melanoma
Moderna and Merck have jointly designed an mRNA-based vaccine against advanced melanoma.19 The vaccine has also received encouraging results.
In the news
Meanwhile, a phase II clinical trial of pancreatic cancer mRNA vaccines commenced at MSKCC in August 2023 with a larger cohort of 80 patients.20 Follow-up in the news regarding additional findings from both cancer vaccines will be forthcoming.
