Benjamin Schrank, Radiation Oncology Resident at
Authors: Benjamin R. Schrank, Yifan Wang, Annette Wu, Nhat Tran, DaeYong Lee, Jared Edwards, Kristin Huntoon, Shiyan Dong, JongHoon Ha, Yifan Ma, Adam J. Grippin, Seong Dong Jeong, Abin Antony, Mengyu Chang, Minjeong Kang, Thomas D. Gallup, Albert C. Koong, Jing Li, Kyuson Yun, Betty Y. S. Kim, Wen Jiang
“New paper in Nature Cancer!
We engineered an antibody-toxin conjugate (ATC) that enhances immune recognition of tumors by harnessing bacterial mechanisms.
The challenge: Tumor cells are phagocytosed by macrophages. Then, tumor DNA is sensed via cytosolic nucleic acid sensors. This process facilitates antitumor immunity, yet faces two major obstacles: 1) ‘don’t eat me’ signals, including CD47, which block tumor cell phagocytosis, and 2) phagolysosomal sequestration of engulfed tumor DNA within macrophages.
We designed CD47-LLO, an ATC that combines anti-CD47 with a bacterial toxin (Listeriolysin O, LLO), to overcome this barrier.
How it works:
Key findings:
CD47-LLO turns ‘cold’ tumors ‘hot’!
Why this matters:
Most ADCs try to destroy cancer cells by delivering cytotoxic drugs. CD47-LLO harnesses the immune system to recognize and destroy cancer, creating long-term immune memory.
A new frontier for antibody-based cancer immunotherapy? We think so!”
