2.12. The unfulfilled promise of cancer vaccines

Therapeutic cancer vaccines have had a long and chequered history. The BCG (Bacillus Calmette-Guérin) vaccine, originally developed to protect against tuberculosis in the 1920s, was adopted back in the 1970s as treatment for bladder cancer. When delivered locally to the organ, it elicits an anti-tumor immune response.

Progress in recent decades has been painfully slow, however. Only a clutch of therapeutic cancer vaccines has gained approval, and their performance has been decidedly mixed. Provenge (sipuleucel-T), originally developed by Dendreon Corp., exemplifies the field’s unfulfilled promise. The dendritic cell therapy was approved in prostate cancer fifteen years ago on the basis of a four-month survival benefit in clinical trials.  It supposedly ‘trained’ patients’ immune systems to attack their tumors. But its high cost and complicated manufacturing process were its undoing.

More recently, Gritstone Bio spooked investors with lacklustre data from a phase 2 trial in colorectal cancer of its Granite cancer vaccine. Its individualised approach involved presenting to each patient’s immune system up to 20 (tumor-derived) neoantigens, in a prime-boost strategy based on a modified adenovirus vector and a self-amplifying RNA construct. But Candel Therapeutics is currently riding high on the back of promising survival data in pancreatic cancer for CAN-2409. BioNTech has also reported good, albeit early stage, pancreatic cancer data from an mRNA vaccine it is developing with Genentech. Its great mRNA rival Moderna is further advanced with V940 (mRNA-4157), which it is developing with Merck. It has shown promising survival benefits in melanoma, and a late-stage trial in that indication is underway, and the partners have also commenced a phase 3 study in lung cancer.

Companies mentioned in this episode: 
Amgen, BioNTech, Candel Therapeutics, Curevac, Dendreon Corp., Genentech, Gritstone Bio, Iovance Biotherapeutics, Merck, Moderna & Northwest Biotherapeutics. 

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