Bottle of Vaccine, treatment of Cancer (© Giovanni Cancemi - stock.adobe.com)
NASHVILLE, Tenn. — Henry Ford once said failure is simply the opportunity to begin again, and researchers at Vanderbilt University have taken this quote to heart. Previously, researchers developed a cancer vaccine that failed to help stop the growth of advanced tumors. However, rather than discarding their work and starting from the drawing board again, they’re using a second chance to test this vaccine on newly developed tumors.
Their new mouse study published in the Journal for ImmunoTherapy of Cancer found the cancer vaccine helped stop tumors targeting immune cells from growing when injected in the tumors’ early stages. While other clinical trials test cancer vaccines, this is one of the few studies not focused on advanced tumors. According to the study authors, the timing of vaccination is critical to seeing results.
“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,” says Dr. Mary Philip, an associate director of the Vanderbilt University’s Institute for Infection, Immunology, and Inflammation and senior study author, in a media release. “There are not many cancer studies where mice have been followed so long after vaccination and remain tumor-free for two years.”
The new cancer vaccine also helped stop tumors from growing when another type of cancer treatment called immune checkpoint blockade (ICB) was ineffective. ICB therapies are usually given for advanced cancer cases. However, only a small group of patients with specific cancer types achieved remission after this treatment.
“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,” explains Dr. Philip. “The vaccination boosts the T cells into a functional state so that they can eliminate early cancer cells.”
The team created a genetic cancer mouse model that would reflect a person’s liver cells becoming cancerous. The vaccine boosted the power of cancer-fighting immune cells, but only if the tumors were in an early stage and not advanced state.
The vaccine was previously tested in human clinical trials for advanced cancers. It uses a gram-positive intracellular bacterium to trigger strong CD4 and CD8 T cell responses. The vaccine also expresses signs of tumors, which makes tumor-reactive T cells more sensitive to signs of cancer.
Vaccinated mice at an early stage were free of tumors, although the vaccine did not help slow down liver tumor progression when administered 100 days later. Overall, the researchers found the presence of reactive immune cells — specifically progenitor TCF1+tumor-specific CD8 T cell populations — is needed for cancer vaccines to work.
Paper Summary
Methodology
In this study, researchers used a special type of mouse model where liver cells randomly turn cancerous. To test how effective the immune system can be against cancer, they focused on a type of immune cell called CD8 T cells, which are known to attack tumors. The mice were divided into two groups: one with early-stage tumors and another with advanced tumors. They gave some mice a cancer vaccine while others received different treatments like immune checkpoint blockade (ICB). They then studied how the CD8 T cells behaved in the mice—whether they stayed functional or became less effective over time—and how the treatments influenced cancer growth.
Key Results
The researchers found that the vaccine helped the immune system fight cancer, especially in the early stages. The vaccinated mice had immune cells that stayed strong and kept fighting off the cancer for a long time. These special immune cells could renew themselves, which means they stay ready to attack the cancer whenever needed. On the other hand, the mice that didn’t get the vaccine, or those treated with other methods like ICB, didn’t do as well. Their immune cells got tired and couldn’t stop the cancer from growing.
Study Limitations
Although the study showed that the vaccine worked well in mice with early-stage cancer, it might not be as effective for later stages of cancer. The study was also done in mice, which means the results might not be exactly the same for humans. More research is needed to understand how this approach works in different kinds of cancers and in people.
Discussion & Takeaways
The study suggests that giving a cancer vaccine early, before tumors are too advanced, can help the immune system fight the disease better. The vaccine helped create a special type of immune cell that could keep attacking the cancer for a long time. This is important because it shows that vaccines might work best if they’re given early when the immune system is still strong. The findings could lead to new cancer treatments, especially for people at risk of developing cancer or those with early-stage cancer.
Funding & Disclosures
This research was supported by grants from the National Institutes of Health (NIH) and other organizations. The researchers involved also acknowledge contributions from several core facilities and services at Vanderbilt University Medical Center. No conflicts of interest were declared by the authors, and the study was approved by Vanderbilt’s Institutional Animal Care and Use Committee.
