The light at the end of the tunnel.

“Cancer thrives when it’s able to hide in the dark corners of the human body, unseen by the natural immune system,” says Sidi Chen, PhD, assistant professor in the Yale University School of Medicine Department of Genetics, Systems Biology Institute and Cancer Center (West Haven, CT).  

“Metaphorically, I’m shining a bank of lights on cancer cells to enable the immune system’s defenses to find them and destroy them.” 

“Traditional cancer treatments are relatively simple, but cancer is a complex disease that may need more sophisticated therapies,” says Dr. Chen who is using funding from Alliance for Cancer Gene Therapy to advance a versatile and highly scalable strategy he’s been developing and calling MAEGI — Multiplexed Activation of Endogenous Genes as an Immunotherapy. 

“By understanding the biology of cancer at the cellular and molecular levels, cancer researchers have learned a lot about how cancer thrives, which has revealed opportunities for how it can be stopped,” says Dr. Chen. “We identify what it is that makes cancer cells different from healthy cells and we stimulate the immune system’s cells to target those differences, to kill the cells that exhibit those differences. 

“Cell and gene therapies that leverage this natural power of the immune system are extending lives and improving quality of lives,” says Dr. Chen. “A number of approaches are being tested and employed today, such as checkpoint blockades, adoptive cell transfers, recombinant cytokines and cancer vaccines. All of these offer promise in the fight against solid tumors, but none are perfect. Only a fraction of patients who receive these therapies realize sustainable outcomes. 

“The challenge is that cancers and immune systems function differently from person to person. There is no single solution,” and this is what makes Dr. Chen’s MAEGI technology unique and exciting. In the Chen Laboratory at Yale, Dr. Chen puts the Multiplexed Activation into MAEGI by simultaneously targeting multiple differences and activating multiple immune system responses. 

“It’s like having an entire search party instead of just one guy with a flashlight,” says Dr. Chen about MAEGI. 

MAEGI has proven very effective in animal studies and its initial success is documented in the November 2019 issue of Nature Immunology. “With the Alliance’s generous support, I hope to translate this success into the clinic to combat today’s most difficult-to-treat cancers, such as pancreatic cancer here in this project, or extending to other aggressive cancers like melanoma, glioblastoma and triple negative breast cancer,” says Dr. Chen. 

This Alliance for Cancer Gene Therapy Research Fellow is funded by Swim Across America.