Adding a personalized antitumor vaccine to the PD-1 inhibitor pembrolizumab may be safe and about twice as effective at shrinking tumors in patients with hepatocellular carcinoma compared with pembrolizumab alone, according to new findings presented by Yarchoan et al at the American Association for Cancer Research (AACR) Annual Meeting 2024 (Abstract 1191/25) and simultaneously published in Nature Medicine.
Background
Hepatocellular carcinoma—the most common type of hepatic cancer and one of the leading causes of cancer-related mortality worldwide—has a 5-year survival rate of less than 10% postdiagnosis. Although current immunotherapies such as PD-1 inhibitors aim to reduce the restraints cancer cells place on the immune system, the treatments have limited effects.
However, recent advances in cancer vaccines have overcome challenges in their development and may present new opportunities to treat hepatocellular carcinoma. Previous studies have demonstrated that personalized cancer treatments may prevent cancer recurrence in patients who had surgery to remove skin or pancreatic tumors.
“We are at an exciting time in new therapy development. Personalized vaccines are the next generation of vaccines that are showing promise in treating difficult cancers when given with immune checkpoint therapy,” highlighted co–study author Elizabeth Jaffee, MD, the Dana and Albert “Cubby” Broccoli Professor of Oncology, Deputy Director of the Sidney Kimmel Comprehensive Cancer Center, and Director of the Convergence Institute at Johns Hopkins University.
To develop the personalized antitumor vaccine, the researchers used tumor biopsy cells to identify cancer-associated genetic mutations in the tumors. They utilized a computer algorithm to determine which of the mutated genes produce proteins the immune system can recognize. They then manufactured the personalized vaccine containing the DNA for the selected mutated genes—each of which included up to 40 genes. The vaccine was designed to help the immune system recognize the abnormal proteins encoded in the selected genes and destroy cells producing them.
Study Methods and Results
In the new preliminary clinical trial, researchers assigned 36 patients with hepatocellular carcinoma to receive pembrolizumab in combination with the personalized antitumor vaccine.
The researchers found that nearly one-third of the patients saw their tumors shrink—which was about twice as many patients as seen in previous studies in which patients with hepatocellular carcinoma were treated with anti–PD-1 therapy alone—and about 8% of them experienced a complete response.
The researchers reported that the most common adverse effect associated with the vaccine was a mild injection-site reaction, and there were no serious adverse events.
The researchers emphasized that combining the personalized antitumor vaccine with pembrolizumab may help revive immune T cells that have become exhausted as well as recruit a fresh set of T cells to target the specific mutant proteins in the tumors. After evaluating tumor biopsy samples collected postvaccination, the researchers discovered evidence that T cells were created and subsequently traveled to and attacked the tumor cells. They also found that the patients who received vaccines targeting the greatest number of mutant proteins had the most favorable responses.
Conclusions
The researchers underscored that that personalized antitumor vaccines may be effective at shrinking or eliminating established cancer cells and could be used to treat other types of cancers. They hope their new findings can lead to the development of more effective personalized antitumor vaccines.
“The study provides evidence that a personalized [antitumor] vaccine can enhance clinical responses to anti–PD-1 therapy. A larger randomized clinical trial will be needed to confirm this finding, but the results are incredibly exciting,” underlined lead study author Mark Yarchoan, MD, Associate Professor of Oncology at the Johns Hopkins University School of Medicine. “The role of personalized [antitumor] vaccines is expanding,” he concluded.
Disclosure: The trial was sponsored by Geneos Therapeutics. For full disclosures of the study authors, visit abstractsonline.com and nature.com.
