Innovative Approach to Combat Leukemia by Disrupting Cancer Cell Signaling

Researchers at the Medical University of South Carolina's Hollings Cancer Center have made a breakthrough in leukemia treatment by identifying and targeting a critical signaling loop responsible for the growth and survival of leukemia cells. Published in Nature Communications, this study unveils how disrupting the loop between the protein IL-33 and its receptor IL1RL1 can weaken the protective environment around leukemia stem cells, making them more vulnerable to treatment.

Leukemia, particularly acute myeloid leukemia (AML), is notorious for its aggressive nature and tendency to relapse even after standard therapies. A key challenge is the disease's ability to hide in the bone marrow through leukemia stem cells that evade chemotherapy. These cells, supported by a feedback loop involving IL-33 and IL1RL1, promote tumor growth and create an immune-suppressive microenvironment that shields the cancer.

To overcome this, the research team developed a novel bispecific antibody immunotherapy. This innovative treatment simultaneously blocks the IL-33/IL1RL1 signaling and activates T-cells like CD8+ to attack the leukemia cells directly. In preclinical models, this dual-action antibody effectively destroyed leukemia cells, dismantled their protective immune barriers, and slowed disease progression. Remarkably, the therapy led to improved survival rates without significant side effects.

Dr. Sophie Paczesny, the lead researcher and co-chair of the Cancer Biology and Immunology Research Program, emphasized the potential of this approach. She highlighted that IL1RL1 is also expressed in other cancers, including colorectal, lung, ovarian, and brain tumors, suggesting that this strategy could have broad applications. The treatment’s reduced toxicity and easier manufacturing process compared to current therapies could make it a safer, more accessible option for patients.

This research marks an important step toward targeted immunotherapy that not only kills cancer cells but also dismantles the immune defenses they exploit. While further clinical trials are necessary, such treatments could revolutionize care for AML and potentially other cancers with similar microenvironmental features, offering new hope for cases resistant to existing therapies.

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