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MIT research found new targets for future cancer vaccines.
Targeting certain proteins found on cancer cells, vaccination can help enhance the T cell’s response to tumors.
In the past decade, scientists have been exploring vaccines as a way to help fight cancer. These experimental cancer vaccines are designed to stimulate the body’s own immune system to destroy tumors by injecting cancer protein fragments found on tumors.
So far, none of these vaccines have been approved by the FDA, but some vaccines have shown promise in the treatment of melanoma and certain types of lung cancer in clinical trials . Researchers from the Massachusetts Institute of Technology (MIT) found that vaccination against certain cancer proteins can increase the overall T cell response in mice and help shrink tumors. This new discovery may help researchers decide what to include in a cancer vaccine protein.
The research team found that vaccination against the types of proteins they identified can help awaken the dormant T cell population against these proteins and strengthen the overall immune response.
“This study emphasizes the importance of in-depth exploration of the details of the anti-cancer immune response. We can now see that not all anti-cancer immune responses are equal, and vaccination can produce a powerful response to a target that has been effectively ignored. ,” Tyler Jacks said.
Megan Burger, a postdoctoral fellow at MIT, is the lead author of the new study, which was published in the journal Cell on September 16, 2021.
T cell competition
When cells start to become cancerous, they begin to produce mutant proteins that are not seen in healthy cells. These cancerous proteins, also called neoantigens , can alert the body’s immune system that something is wrong, and T cells that recognize these neoantigens begin to destroy cancer cells.
Eventually, these T cells will experience a phenomenon called ” T cell exhaustion “, which occurs when the tumor creates an immunosuppressive environment that disables T cells and causes the tumor to grow uncontrollably. Phenomenon.
Scientists hope that cancer vaccines can help restore the vitality of these T cells and help them attack tumors. In recent years, they have been committed to developing methods to identify neoantigens in patient tumors and incorporate them into personalized cancer vaccines. Some of these vaccines have shown promise in the treatment of melanoma and non-small cell lung cancer in clinical trials.
Burger said: “These therapies have played an amazing role in a small number of patients, but the response of most patients is still not very good. A lot of research in our laboratory is to understand why this is the case and what we can do. To get more patients to respond.”
Previous studies have shown that only a small percentage of the hundreds of neoantigens found in most tumors can produce T cell responses.
This new MIT study helps explain why this is the case. In the study of mice with lung tumors, the researchers found that with the emergence of tumor-targeted T cells, T cell subsets targeting different cancer proteins compete with each other, eventually leading to a dominant T cell population. Appear. After these T cells are exhausted, they remain in the environment and inhibit any competing T cell populations for different proteins found on the tumor.
However, Burger found that if she vaccinated these mice with neoantigens targeted by suppressed T cells, she could rejuvenate these T cell populations.
She said: “If you vaccinate against an antigen that suppresses the response, you can release these T cell responses. Trying to identify these suppressed responses and targeting them specifically may improve the patient’s response to vaccine treatment.”
In this study, the researchers found that they had the highest success rate when they were vaccinated with neoantigens, and that neoantigens bind weakly to the immune cells responsible for submitting antigens to T cells. When they injected mice with lung tumor vaccines with one of these new antigens, they found that the tumors shrank by an average of 27%.
Burger said: “T cells proliferate more and they can better target tumors. We have seen in our mouse model that as a result of treatment, the burden of lung tumors has been reduced overall.”
After vaccination, the T cell population includes a cell with the potential to continue to replenish the response, which may allow the tumor to be controlled for a long time.
In future work, the researchers hope to test treatments, combining this vaccination strategy with cancer drugs called checkpoint inhibitors, which can stop tired T cells from working and stimulate them to attack tumors. The findings published today support this view, and the results also show that vaccination increases the number of a specific type of T cell that has been shown to respond well to checkpoint therapy.
Antigen dominance hierarchies shape TCF1+ progenitor CD8 T cell phenotypes in tumors by Megan L. Burger, Amanda M. Cruz, Grace E. Crossland, Giorgio Gaglia, Cecily C. Ritch, Sarah E. Blatt, Arjun Bhutkar, David Canner, Tamina Kienka, Sara Z. Tavana, Alexia L. Barandiaran, Andrea Garmilla, Jason M. Schenkel, Michelle Hillman, Izumi de los Rios Kobara, Amy Li, Alex M. Jaeger, William L. Hwang, Peter M.K. Westcott, Michael P. Manos, Marta M. Holovatska, F. Stephen Hodi, Aviv Regev, Sandro Santagata and Tyler Jacks, 16 September 2021, Cell.
MIT research found new targets for future cancer vaccines
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