A cancer vaccine, previously unsuccessful in clinical trials involving patients with advanced tumors, has shown potential efficacy when administered earlier in the treatment cycle, according to a new study by Vanderbilt researchers. The study, published in the Journal for ImmunoTherapy of Cancer, indicates that the vaccine can effectively block tumor progression in a mouse model when applied at the early stages of lesion development.
The research team discovered that mice with early-stage lesions possess tumor-specific T cell populations that can be therapeutically exploited through vaccination. This contrasts with mice bearing advanced tumors, which lack these T cells. This approach differs significantly from most cancer vaccine studies, which have historically focused on patients with advanced-stage cancers.
Key Findings
"Our study suggests that the timing of vaccination is important," said Mary Philip, MD, PhD, associate director of the Vanderbilt Institute for Infection, Immunology and Inflammation and the study’s senior author. The study utilized a clinically relevant genetic cancer mouse model where hepatocytes (liver cells) sporadically undergo oncogenic transformation. Researchers observed that mice with early lesions retained a progenitor TCF1+tumor-specific CD8 T cell population, a characteristic not found in mice with advanced tumors.
The vaccine, previously tested in human clinical trials for advanced cancers, employs a gram-positive intracellular bacterium engineered to express the tumor epitope, thereby boosting tumor-reactive T cells. In the study, all mice vaccinated at an early stage remained tumor-free, while the vaccine failed to impede liver tumor progression when administered later (at 100 days of age).
Overcoming Immune Checkpoint Blockade Resistance
Notably, early treatment with the cancer vaccine effectively blocked tumor progression even when immune checkpoint blockade (ICB) therapies proved ineffective. ICB therapies, while approved for treating advanced cancers, only induce durable remission in a subset of patients with specific cancer types.
"ICB works by taking the brakes off T cells, but if the T cells have never been properly activated, they are like cars without gas, and ICB doesn’t work," Philip explained. "The vaccination boosts the T cells into a functional state so that they can eliminate early cancer cells."
Implications for Future Research
The researchers concluded that the presence of a progenitor TCF1+tumor-specific CD8 T cell population is crucial for the effectiveness of cancer vaccines. This finding supports further investigation into vaccine strategies that aim to achieve long-term, progression-free survival for a broader range of cancer patients.
"A unique feature of our study is that these mice are at high, essentially 100% risk of developing cancers, so the fact that a single immunization at the right time can give lifelong protection is pretty striking. There are not many cancer studies where mice have been followed so long after vaccination and remain tumor free for two years," Philip added.
