Researchers at Columbia Engineering have unveiled a groundbreaking cancer therapy that utilizes bacteria to sneak viruses into tumors. This innovative approach could revolutionize treatment for solid tumors.
In a landmark study published in Nature Biomedical Engineering, Columbia Engineering researchers have introduced a novel cancer therapy that leverages the synergistic capabilities of bacteria and viruses to infiltrate and destroy tumors. This innovative platform, named CAPSID (Coordinated Activity of Prokaryote and Picornavirus for Safe Intracellular Delivery), shows promise in overcoming significant obstacles in cancer treatment.
The interdisciplinary team, led by Tal Danino, an associate professor of biomedical engineering at Columbia Engineering, in collaboration with virology expert Charles M. Rice from The Rockefeller University, has demonstrated the therapy’s effectiveness in mouse models.
“This is probably our most technically advanced and novel platform to date,” Danino said in a news release.
The new approach ingeniously combines the tumor-targeting nature of Salmonella typhimurium with the cancer-killing efficiency of an engineered virus.
One of the major challenges in oncolytic virus therapy is the immune system’s ability to neutralize these viruses before they reach the tumor. The solution devised by the Columbia team is a biological sleight of hand: using tumor-seeking bacteria to conceal and transport the virus safely to the tumor.
“The bacteria act as an invisibility cloak, hiding the virus from circulating antibodies, and ferrying the virus to where it is needed,” added co-lead author Zakary S. Singer, a former postdoctoral researcher in Danino’s lab.
The bacteria’s role doesn’t end at camouflaging the virus. Once the bacteria infiltrate the tumor’s low-oxygen, nutrient-rich environment, they invade cancer cells and release the viral payload directly inside.
“We programmed the bacteria to act as a Trojan horse by shuttling the viral RNA into tumors and then lyse themselves directly inside of cancer cells to release the viral genome, which could then spread between cancer cells,” Singer added.
The inherent restriction of bacterial movement means the viral component remains localized within the tumor, a significant safety feature of the system.
Another safeguard ensures that the virus cannot spread beyond the tumor, as it relies on a bacterial-derived molecule found only within the tumor environment.
“Spreadable viral particles could only form in the vicinity of bacteria, which are needed to provide special machinery essential for viral maturation in the engineered virus, providing a synthetic dependence between microbes,” added Singer.
This dual containment approach mitigates the risk of systemic spread, a crucial aspect for eventual clinical application.
Looking towards the future, the researchers are working to bring this revolutionary therapy to the clinic.
“As a physician-scientist, my goal is to bring living medicines into the clinic,” added co-lead author Jonathan Pabón, an MD/PhD candidate at Columbia.
Efforts are underway to test the approach across various cancers and develop a versatile toolkit of viral therapies tailored to specific cellular conditions.
Danino, Rice, Singer and Pabón have also filed a patent application related to this groundbreaking work, marking a significant step toward clinical translation.
Source: Columbia University School of Engineering and Applied Science