Cell: MIT research discovers new targets for future cancer vaccines

Targeting specific proteins found on cancer cells, vaccines can help enhance the response of T cells to tumors

For the past decade, scientists have been exploring vaccines to help fight cancer

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

The research team found that vaccines targeting the types of proteins they identified can help awaken the population of dormant T cells that target 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

T cell competition

When cells start to become cancerous, they begin to produce mutant proteins that are not seen in healthy cells

Eventually, these T cells will experience a phenomenon called "T cell exhaustion", which occurs when the tumor creates an immunosuppressive environment that makes the T cells lose their function and causes the tumor to grow uncontrollably

Scientists hope that cancer vaccines can help restore the vitality of these T cells and help them attack tumors

Berg 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

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 happens

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

Reduce tumors

In this study, the researchers found that when they were vaccinated with neoantigen vaccines, the success rate was highest, and the neoantigens were weakly bound to immune cells responsible for submitting antigens to T cells

Berg said: "The more T cells proliferate, they can better target tumors

After vaccination, the T cell population includes a cell with the potential to continue to supplement the response, which may allow the tumor to be controlled for a long time

In future work, the researchers hope to test treatments that combine this vaccination strategy with cancer drugs called checkpoint inhibitors, which can stop tired T cells from working and stimulate them to attack tumors
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The findings published today support this view.
The findings also show that vaccination increases the number of a specific type of T cell that has been shown to respond well to checkpoint therapy
.

references:

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 MK Westcott, Michael P.
Manos, Marta M.
Holovatska, F.
Stephen Hodi, Aviv Regev, Sandro Santagata and Tyler Jacks, September 16, 2021, Cell
.
DOI: 10.
1016 / j.
cell.
2021.
08.
020

MIT research discovers new targets for future cancer vaccines