A new multinational study led by Dr. Poul Sorensen, distinguished scientist at BC Cancer Research Institute, professor in the UBC Faculty of Medicine and holder of the Johal Chair in Childhood Cancer Research, has been published in Cancer Discovery, a leading journal of the American Association for Cancer Research.
The research, conducted principally by Dr. Haifeng Zhang from the Sorensen Lab, describes a targeted immunotherapy treatment that uses antibody–drug conjugates (ADCs) to specifically target cancer cells displaying IL1RAP, a protein found on the surface of multiple fusion-driven cancers including Ewing sarcoma, anaplastic large cell lymphoma and other malignancies.
“Fusion proteins are oncogenic drivers that are generated when sequences between two genes, usually from different chromosomes, become fused together after genomic alterations in tumor cells, creating new proteins with cancer-causing capacity,” says Dr. Sorensen. “While the fusion proteins themselves can be difficult to target, we found that different fusions directly activate production of IL1RAP, creating a new targeting approach using ADCs that search out and deliver drugs to tumor cells expressing IL1RAP.”
The study shows that ADCs targeting IL1RAP can selectively eliminate cancer cells in both primary and metastatic disease, while sparing healthy cells and reducing cancer spread. Because IL1RAP is almost never found in healthy tissues, the treatment demonstrated very encouraging safety results.
“We are excited about the potential of bringing IL1RAP ADCs to the clinic for treating Ewing sarcoma, as outcomes for patients with metastatic disease have not improved for decades, and the ADCs appear to be very potent while the toxicity profiles are highly favorable,” Dr. Sorensen explains. “Moreover, since IL1RAP appears to be expressed in a number of other tumor types, including acute myeloid leukemia, the potential is for this targeting strategy to be applicable to many different tumor types.”
By identifying a shared vulnerability across multiple fusion‑driven cancers, this study highlights IL1RAP as a promising treatment target and supports further clinical testing of ADC‑based therapies for patients with aggressive and hard‑to‑treat cancers.
This work was made possible with generous funding support from the BC Cancer Foundation.
Congratulations to Dr. Sorensen!
Read the study: IL1RAP antibody-drug conjugates potently target primary and metastatic disease in multiple oncofusion-driven cancers