Newly discovered class of molecules may boost cancer vaccine development

Cancer vaccines are designed to heighten the immune system's awareness of a tumor's unique features, boosting its ability to recognize, attack, and destroy the cancer. 

To date, effective cancer vaccines have focused on what are called "neoantigens," tumor-specific peptides that result from acquired mutations.  But not every tumor produces distinct antigens that the immune system can recognize. As a result, current cancer vaccines don't work for all patients.

Now, a team led by researchers in the lab of Broad Cancer Program associate member and Dana-Farber Cancer Institute oncologist Eliezer Van Allen demonstrate the presence of an entirely new class of neoantigens.

Dubbed "retained intron neoantigens," these potential immune triggers stem from short segments of noncoding DNA within genes – called introns – that are typically spliced out when genes are translated into proteins. In cancer, however, introns often get translated into a gene's final protein product.

The team developed and applied an algorithm that could identify these retained introns from 48 melanoma patients who had been treated with a form of cancer immunotherapy called a checkpoint inhibitor. By including retained introns in their analysis, the team roughly doubled the number of neoantigens they could identify. These new peptides, they found, bind to a molecule called MHC class I – the first step toward being recognized by the immune system.