Study: Cancer Vaccines Should Target Long-Lasting T Cells

Although T cells fight off pathogens and diseases, some are stronger and longer lasting than others. The authors of a study published by Cancer Immunology Research suggest that novel cancer vaccines should target T cells that are powerful over a long period of time.

There are 2 types of T cells that are activated by alpha-fetoprotein, an antigen secreted by liver cancer. In the study, the authors found that one of the types of cells is powerful initially, while the other type is more powerful in the long term, according to the study.

“You poke one and it runs. The other you must give a big push,” said corresponding author Dr. Yukai He, MD, PhD.

In a typical immune response, dendritic cells show a suspicious molecule to receptors on T cells, which launches an attack. These cells are powerful antigen presenters, according to the authors.

While the sensitivity and strong response to alpha-fetoprotein from the T cell Tet‌₂₁₂ is good, the authors discovered that the cell was quickly exhausted from prolonged immersion in the antigen and died, according to the study.

“Basically, with a tumor it’s like jumping into a pool of antigen,” Dr He said. “If you are very sensitive to the antigen, you are going to make yourself over reactive and exhausted.”

Although more antigen was needed to alert Tet₄₉₉, the T cell created a stronger and longer anti-cancer attack, according to the study.

This type of T cell also had more stem-like T cells, which allowed for countless replication. The authors said that only 1% to 2% of T cells have this ability, making Tet₄₉₉ ideal for a cancer vaccine.

In animal studies, the authors found that Tet₄₉₉ receptors were weaker, which could explain why more antigens were needed to launch an immune attack. The weakened receptors are also what helped the cells avoid exhaustion and death in the fight against cancer, according to the study.

While the vigorous approach of Tet₂₁₂ may be effective against shorter infections, such as influenza, it may not be ideal against long-term conditions, including cancer or HIV, according to the study.

The authors report that additional studies are needed to determine why the cells respond differently to tumors.

The authors hope to develop a vaccine that increases the level of Tet₄₉₉ and/or related cells to fight cancer.

“We have to find a way in order for cancer vaccines to succeed,” Dr He said.

Numerous cancer vaccines are in development, but there are significant hurdles to overcome to achieve success. The authors note that vaccines are designed to harness the immune system, while cancer suppresses it and older or sick patients generally have weakened immune systems, making it difficult for a vaccine to be effective.

“Our current study points out that our immune system needs to be trained just right so that the immune fighters can persist in the malicious tumor environment and win the war,” Dr He said.