Tweaking（捏，扭） a protein expressed by most liver cancer cells has enabled scientists to make a vaccine¹ that is exceedingly effective at preventing the disease in mice. Alpha-Fetoprotein, or AFP -- normally expressed during development and by liver cancer cells as well -- has escaped attack in previous vaccine iterations（迭代次数） because the body recognizes it as "self," said Dr. Yukai He, immunologist at the Medical College of Georgia and Georgia Regents University Cancer Center.

 

Liver cancer is among the fastest-growing and deadliest cancers in the United States with a 17 percent three-year survival rate. Vaccines² help direct the immune system to attack invaders³ by showing it a representative substance, called an antigen（抗原）, that the body will recognize as foreign, in this case, AFP for liver cancer.

 

In a process called antigen engineering, He tweaked AFP just enough to get the immune system to recognize it but still keep the AFP expressed by liver cancer cells in the bull's eye, he and his colleagues report in the journal Hepatology（肝脏病学）.

 

AFP is expressed by about 80 percent of most common liver cancer cells but not typically by healthy adults. For cancer to flourish, cells must revert⁴ to an immature⁵ state, called dedifferentiation, which is why liver cancer cells express a protein during development and why the immune system can recognize AFP as "self."

 

He's modified AFP was delivered in a vehicle with a proven record for getting into cells. The lentivector（载体） is the backbone⁶ of the human immunodeficiency virus, or HIV, minus most of its genes⁷. It is particularly good at targeting dendritic cells, whose job is to show the immune system antigens then activate⁸ T cells to attack.

 

In a proven model where mice are exposed to chemicals known to induce liver cancer, the vaccine blocked cancer about 90 percent of the time. Mice receiving the vaccine had more T cells generally and more that targeted AFP, which could keep an eye out for re-emerging liver cancer.

 

Recurring⁹ tumor¹⁰ cells is an unfortunately realistic scenario¹¹ for liver cancer patients, who have a 70 percent recurrence¹² rate in five years, He said. Patients typically have surgery to remove the diseased portion of the liver, but there are currently no effective adjuvant therapies, such as chemotherapy, to reduce recurrence, He said.

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