Adding a personalized anti-tumor vaccine to standard immunotherapy is safe and about twice as likely to shrink cancer as standard immunotherapy alone for patients with hepatocellular carcinoma, the most common type of liver cancer, according to a clinical trial led by researchers at the Johns Hopkins Kimmel Cancer Center and its Convergence Institute.
The study was published April 7 in Nature Medicine, with findings also presented at 1:30 p.m. PT at the annual meeting of the American Association for Cancer Research.
A preliminary clinical trial led by Kimmel Cancer Center investigators shows that adding a personalized anti-tumor vaccine to PD-1 inhibitor therapy may improve patient outcomes. The study enrolled 36 patients with HCC. All patients received the PD-1 inhibitor pembrolizumab in combination with a personalized anti-tumor vaccine. The most common adverse effect associated with the vaccine was mild injection site reactions. There were no serious adverse events. Nearly one-third of the patients treated with the combination therapy saw their tumors shrink—about twice as many patients as seen in studies of anti-PD-1 therapy alone in HCC. About 8% had a complete response with no evidence of tumor left after the combination treatment.
To make personalized cancer vaccines, scientists take tumor biopsy cells to identify cancer-associated genetic mutations in the tumor. The scientists use a computer algorithm to determine which of the mutated genes produce proteins the immune system can recognize. Then, scientists manufacture a personalized vaccine containing the DNA for the selected mutated genes. Each vaccine may include up to 40 genes. The vaccine helps the immune system recognize the abnormal proteins encoded in the selected genes and destroy cells producing them.
Combining the personalized vaccine with the PD-1 inhibitor provides a one-two punch to the tumor. The PD-1 inhibitor helps revive immune cells, called T-cells, in the tumor that have become exhausted and unable to destroy the tumor cells. The personalized vaccine calls in the cavalry, helping recruit a fresh set of T-cells that target the specific mutant proteins in the tumor.
When the research team evaluated tumor biopsy samples taken from the study participants after they received the vaccine, they found evidence that T-cells were created in response to the vaccine that travelled to the tumor and attacked tumor cells. They also found that patients who received vaccines targeting the greatest number of mutant proteins had the best responses. This finding may help scientists create even more effective personalized cancer vaccines.
