IL1RAP-specific T cell engager depletes acute myeloid leukemia stem cells

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Interleukin-1 receptor accessory protein (IL1RAP) is highly expressed on acute myeloid leukemia (AML) blasts and leukemic stem cells (LSCs).
• IL1RAP expression is notably absent on normal hematopoietic stem cells (HSCs), presenting a selective therapeutic target.
• Targeting IL1RAP offers a strategy to eliminate AML while preserving normal hematopoiesis.

Purpose of the Study:

• To evaluate the efficacy of BIF002, a novel anti-IL1RAP/CD3 T cell engager (TCE), against AML.
• To characterize the activity of BIF002 in preclinical AML models.

Main Methods:

• BIF002 was generated using Fab arm exchange technology from anti-IL1RAP antibodies.
• Antibodies were isolated from immunized mice using optoelectric positioning and single-cell sequencing.
• The antileukemic activity of BIF002 was assessed in vitro and in vivo using AML cell lines and patient-derived samples.

Main Results:

• BIF002 demonstrated potent T cell activation and lysis of AML cells at subnanomolar concentrations.
• In vivo studies showed BIF002 depleted leukemic cells and significantly prolonged survival in AML xenografts.
• BIF002 effectively eliminated LSCs, preventing disease relapse in secondary recipients.

Conclusions:

• BIF002, a novel anti-IL1RAP/CD3 TCE, shows significant promise for AML treatment.
• The therapy effectively eradicates LSCs and prolongs survival in preclinical AML models.
• BIF002 represents a potential new therapeutic strategy for acute myeloid leukemia.