Patricia Weiser, Pharm.D.
Vaccine technology is rapidly growing in the pharmaceutical industry, with therapy options expanding in response to areas of clinical need. One area of focus is the development of vaccines targeting cancer.
Cancer vaccines generally fall into two categories: preventive and active treatment. Preventive cancer vaccines are currently more established and focus on preventing viral infections associated with future malignancy. Active treatment cancer vaccines, on the other hand, work to help manage existing cancer. These vaccines act on a wide variety of targets, dependent on the type of cancer, location, and even personalized antigens found within an individual’s cancer.
Several active cancer vaccines in the pipeline seem promising. Here is at look at two:
Personalized Vaccine for Melanoma
Merck and Moderna’s personalized mRNA cancer vaccine is currently progressing through the development pipeline. This vaccine, known as mRNA-4157 or V940, utilizes tumor-associated antigens (TAAs) with the intention of generating an immune response toward melanoma cells.
This mRNA vaccine harnesses personalized TAA technology. Biopsies and other tests are completed to determine the exact types of TAAs expressed by an individual’s melanoma cells. Then these specific TAAs, also known as patient-specific neoantigens, are utilized to produce the vaccine. Neoantigens are proteins produced by cancer cells that differ from those produced by healthy cells, making them promising targets.
More specifically, mRNA-4157 consists of personalized mRNA that contains up to 34 different patient-specific neoantigens. In a phase 2 trial, KEYNOTE-942, each patient had a minimum of 9 target epitopes, with 91% of patients receiving mRNA that encoded all 34 epitopes. Nine doses of personalized mRNA-4157 were administered with or without Keytruda (pembrolizumab).
The results revealed that adding the vaccine decreased the risk of post-surgical recurrence or death by 44% compared to Keytruda alone. The vaccine did not cause an increase in immune-related side effects or serious adverse events. The most commonly observed side effects were fatigue, pain at the injection site, and chills.
On the basis of this positive outcome, the FDA awarded breakthrough designation to the vaccine in February 2023. Phase 3 trials are now underway, launched by Merck and Moderna in July 2023.
Personalized mRNA Vaccine Targeting Pancreatic Cancer
BioNTech and Genentech’s autogene cevumeran (also known as BNT122 or RO7198457) utilizes similar technology in an effort to combat pancreatic cancer. This vaccine is composed of 20 patient-specific neoantigens which, after administration, help train the immune system to respond to tumor cells in the pancreas.
The phase 1 trial for autogene cevumeran included additional oncology drugs, including Tecentriq (atezolizumab), Camptosar (irinotecan), and Eloxatin (oxaliplatin). Investigators sought to understand autogene cevumeran’s impact on two outcomes; primarily, they collected data on the immune response and length of response, as well as the clinical outcomes for the patients receiving the therapy.
From an immunological perspective, the vaccine was shown to be capable of successfully generating neoantigen-specific T-cells in 50% of participants. These T cells persisted for up to 2 years, even with post-vaccination chemotherapy.
The effectiveness seems promising as well. Those with an immune response to autogene cevumeran achieved significantly longer periods of time without recurrence of pancreatic cancer. Although the sample size was limited, these findings warrant further investigation into individualized mRNA neoantigen vaccines for pancreatic cancer.
In October 2023, BioNTech announced that Phase 2 studies are underway, with the first patient starting treatment for resected pancreatic ductal adenocarcinoma.
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