A Novel Approach to Cancer Treatment
Researchers at the University of Texas MD Anderson Cancer Center have developed an innovative antibody-toxin conjugate (ATC) designed to stimulate the immune system to eliminate tumors. According to preclinical findings published in Nature Cancer, this approach combines the strengths of antibody-drug conjugates (ADCs) and immunotherapies, offering a potential breakthrough in cancer treatment.
How ADCs Work and Their Limitations
ADCs have revolutionized cancer therapy by precisely targeting cancer cells through specific protein markers. These conjugates deliver a chemotherapy payload directly to tumor cells, leading to their destruction. However, ADCs often fail to eliminate tumors completely, resulting in resistance and recurrence.
Shifting the Strategy: Harnessing the Immune System
Wen Jiang, M.D., Ph.D., associate professor of Radiation Oncology and corresponding author of the study, explained that ATCs function differently from traditional ADCs. “ADCs destroy tumor cells but often do so incompletely, allowing resistance to develop. Our ATC approach, on the other hand, triggers a natural immune response that minimizes side effects while attacking tumors throughout the body and preventing recurrence,” Jiang stated.
Targeting the CD47 “Don’t Eat Me” Signal
Many solid tumors express CD47, a protein that prevents immune cells from attacking them. The newly developed ATC targets CD47 but, instead of delivering chemotherapy, it carries a bacterial toxin.
When the CD47 antibody binds to the tumor, it marks it for destruction by immune cells. Once engulfed, the bacterial toxin activates inside the immune cells, creating pathways that allow tumor DNA and protein fragments to escape. Instead of being destroyed, these fragments train the immune system to recognize and attack similar tumors throughout the body.
Inspiration from Bacteria
“Bacteria have an incredible ability to escape from cellular traps, multiply, and spread while keeping host cells functional. We harnessed this ability to transport intact tumor material to immune cells,” Jiang explained. “This process helps the immune system recognize and attack tumors more effectively.”
Promising Preclinical Results
In breast cancer and melanoma models, this approach successfully trained immune cells to recognize unique cancer cell markers, leading to a robust antitumor response. The activated T cells remained effective even two months after treatment, suggesting a long-term memory effect that could prevent tumor recurrence.
Future Prospects: Combining ATCs with Conventional Therapies
First author Benjamin Schrank, M.D., Ph.D., resident physician in Radiation Oncology, highlighted the broader implications of this research. “We want to train the immune system to recognize tumors and continue fighting cancer even after treatment ends,” Schrank said.
ATCs could also be combined with radiation therapy. Solid tumors often upregulate CD47 in response to radiation, making them even more vulnerable to the ATC approach.
Expanding the Scope of ATCs
Betty Kim, M.D., Ph.D., professor of Neurosurgery and co-lead of the study, emphasized that this immune-stimulating ATC concept extends beyond CD47. “We are already developing ATCs targeting other tumor-specific receptors to treat a wide range of difficult-to-treat cancers,” she said.
A Timeline for Clinical Testing
As reported by MedicalXpress, the research team aims to have the first ATCs ready for clinical trials within three to five years. This breakthrough could open a new chapter in cancer immunotherapy.