MIT sets new targets for cancer vaccines

Vaccination against certain proteins found on cancer cells can help enhance T cell response to tumors

In the past decade, scientists have been exploring vaccines as a way 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 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

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

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.

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

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

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

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 they had the highest success rate when they were vaccinated with neoantigens, and that neoantigens bind weakly to the immune cells responsible for submitting the antigen to T cells

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 overall burden of lung tumors is reduced
.
"

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.
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 MK Westcott, Michael P.
Manos, Marta M.
Holovatska, F.
Stephen Hodi, Aviv Regev, Sandro Santagata and Tyler Jacks, 16 September 2021, Cell .

DOI: 10.
1016/j.
cell.
2021.
08.
020