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milatuzumab-CL2E-SN-38
- Development stage
- Preclinical
- Lead developer
- Gilead Sciences
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
Milatuzumab-CL2E-SN-38 is an experimental antibody-drug conjugate (ADC) developed by Immunomedics (now part of Gilead Sciences). It consists of milatuzumab, a humanized monoclonal antibody targeting CD74, conjugated to the cytotoxic payload SN-38 (the active metabolite of irinotecan) via the CL2E cleavable linker. CD74 is a cell-surface antigen that is highly expressed and rapidly internalized in various hematologic and solid tumors. The CL2E linker is a cathepsin-B sensitive variant designed for exceptional serum stability (half-life of approximately 87.5 days) while allowing for efficient intracellular release of SN-38, a potent topoisomerase I inhibitor, through a two-step process involving enzymatic cleavage and intramolecular cyclization. Preclinical studies have evaluated this conjugate in models of melanoma, pancreatic cancer, hepatoma, gastric cancer, and Burkitt lymphoma.
- Other names
- hLL1-CL2E-SN-38hLL-1-CL2E-SN-38hLL 1-CL2E-SN-38
02
Targets
TOP1 (DNA Topoisomerase I)CD74 (Major histocompatibility complex class II invariant chain)
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