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Image Credit: Anti-tumor vaccine, by Sciworthy (via Canva.com)

Scientists have been developing vaccines to protect against disease for years. Most of these vaccines have been prophylactic, meaning they work by preventing disease. Some vaccines can now also be therapeutic, meaning they are used when someone is already infected with a disease to help eliminate it. Other recent advances include the advent of mRNA vaccines, which work by sending new genetic material into a cell to cause the body’s defense system to be activated. mRNA vaccines have been successful in preventing severe cases of COVID-19, and now they are being researched to eliminate tumors. 

Studies have demonstrated the clinical promise of mRNA vaccines in a range of applications. Yet, using mRNA vaccines to enact an immune response against tumors is still in very early stages. Prior mRNA vaccines used for cancer treatment did not cause a sufficient response in the cells that destroy cancerous cells, known as cytotoxic T-cells. Therefore, the immune system was not able to kill the cancer. When there are enough cytotoxic T-cells, tumors will often reduce in size, which is a positive result for the patient. If researchers can figure out how to trigger a consistently strong response, mRNA vaccines could become a major contributor to reducing cancer growth and saving lives.

A prior study investigated the effect of adding a molecule known as resiquimod to vaccines. This molecule can enhance and prolong a vaccine’s effect by attaching to receptors on immune cells, triggering a strong immune response. 

In this new study, researchers tested a new vaccine recipe to try to cause a strong immune response against a tumor. They did so by encapsulating the mRNA with nanoparticles, which protects the mRNA from being destroyed while traveling to its target. They also incorporated resiquimod to try to enhance the T-cell response. 

The researchers first established that their vaccine was able to cause a strong immune response. They compared their vaccine recipe (mRNA plus resquimod with nanoparticle delivery) to recipes with individual components omitted. They found that the addition of resquimod to the vaccine caused a 50% stronger cytotoxic T-cell response than nanoparticle-packaged mRNA without resquimod.

The researchers then performed two experiments. First, they tested the vaccine’s ability to prevent lymphoma by vaccinating mice 25, 11, and 4 days prior to introducing tumor cells into the mice. They also tested the vaccine on mice that had prostate cancer cells already implanted in them, injecting the mice with the vaccine on the 1st, 11th, and 15th day after implantation. The cells were implanted into the back right side of the mice, so they could measure the tumor daily using calipers. They then dissected the spleen and lymph nodes after 19 or 27 days. 

To determine how many T-cells there were, the researchers ground up the spleen tissue to make sure the sample contained only individual cells, rather than cell clumps Then, they stained the cells with a specific dye and ran them through a machine that lets one cell through at a time, to count cells and detect what kind of cell it is based on the dye. To test how far the T-cells got into the tumor, they dissected the tumor tissue and soaked it in different dyes that stain the T-cells and glow under specific conditions. Following staining, they looked at the tissue under a microscope. An increase in T-cells in the tumor and in general are both positive signs of an immune response to the cancer.

The researchers found that the mice that received the vaccine had a higher percentage of T-cells in the tumor and in general, in both experiments. The mice that were given the vaccine with resquimod after the implantation had tumors that were about half as big as the mice who received a vaccine without resquimod. The tumors were about 4.5 times smaller in the mice that received the vaccine with resquimod prior to having cancer cells implanted in them.

With the addition of the resquimod, researchers found an increase in cytotoxic T-cell response and infiltration along with a decrease in tumor size, meaning that this new vaccine strategy helped to prevent and eliminate lymphoma and prostate cancer in mice. This vaccine strategy should be further tested on different kinds of cancer and eventually in humans to see how effective it truly is in treating and preventing cancer. 

Study Information

Original study: Adjuvant-pulsed mRNA vaccine nanoparticle for immunoprophylactic and therapeutic tumor suppression in mice

Study published on: October 1, 2020

Study author(s): Mohammad Ariful Islam, Jamie Rice, Emma Reesor, Harshal Zope, Wei Tao, Michael Lim, Jianxun Ding, Yunhan Chen, Dike Aduluso, Bruce R. Zatter, Omid C. Farokhzad, and Jinjun Shi

The study was done at: Harvard Medical School (USA)

The study was funded by: Prostate Cancer Foundation (PCF) Young Investigator Award (J.S.), the David Koch-PCF Award in Nanotherapeutics (O.C.F.), and the US National Institutes of Health (NIH) grant CA200900

Raw data availability: The authors declare that all data supporting the findings of this study are available within the paper and its supplementary information.

Featured image credit: Anti-tumor vaccine, by Sciworthy (via Canva.com)