Personalized Cancer Vaccines Face Triple Hurdle: Manufacturing, Cost and Efficacy

Manufacturing, cost and efficacy—not clinical success—are the main barriers to commercializing personalized mRNA cancer vaccines, according to an analysis.

According to BioPharma Dive on the 10th (local time), Merck (MSD) and Moderna’s personalized melanoma vaccine delivered positive results in a phase 3 trial last month, raising industry expectations. But significant hurdles remain before it can be commercialized at scale.

Unlike conventional shots that prevent disease, this personalized treatment trains the immune system to target “neoantigens” found only in an individual patient’s tumor. As a result, each patient needs a different vaccine.

The manufacturing process is also complex and lengthy. A tumor is biopsied and sequenced alongside healthy blood cells; target neoantigens are then selected, and synthetic mRNA encoding them is produced and injected into the patient. The Merck-Moderna vaccine contains up to 34 neoantigens.

At commercial scale, the approach requires “scale-out”—producing tens of thousands of individual batches rather than a single large batch. Patient tracking and batch-specific purification processes are also needed to ensure each patient receives the correct treatment.

Amy Walker, CEO of synthetic DNA manufacturer 4basebio, said, “This is an n-of-1 approach that completely upends conventional manufacturing practices. The key is not ‘scale-up’ but ‘scale-out’—increasing individual production.”

Speed and cost are also obstacles. Walker said patients are “very ill” and that the industry’s target timeline from biopsy to dosing is 6–8 weeks. “We need to get the cost right from the start so that price doesn’t limit access,” she emphasized.

The autologous cellular immunotherapy Provenge for prostate cancer set a precedent. Although it was approved by the U.S. Food and Drug Administration (FDA) in 2010, manufacturing costs approached 77% of its selling price, and it fell short of commercial expectations despite a launch price of $93,000. Its developer, Dendreon, went bankrupt in less than 5 years.

The efficacy hurdle also came into view. Nine days after Merck and Moderna announced their phase 3 success, BioNTech and Genentech discontinued a phase 2 trial of a personalized vaccine for colorectal cancer. The companies said an independent monitoring committee had identified a numerical imbalance in overall survival between the treatment groups and determined that continuing the trial was unlikely to change the efficacy results.

The two trials differed in combination therapy and tumor type. Merck and Moderna combined their vaccine with the immunotherapy Keytruda, while the discontinued trial tested the vaccine as monotherapy. Melanoma is also an immunologically “hot” tumor, whereas colorectal cancer is “cold” and more difficult to treat with immunotherapy.

“Hot tumors have a high mutational burden and are well suited to personalized vaccines, but cold tumors have fewer unique neoantigens, making them much harder to target,” Walker explained.

However, she said the barriers are not insurmountable. “We should be able to improve treatment success rates by identifying new antigens that are more immunogenic,” she said. “I hope data from the many tumor biopsies will eventually help us find common targets for off-the-shelf vaccines.”