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177Lu-A2DM
- Development stage
- Preclinical
- Lead developer
- City of Hope
- Modality
- Antibody-Radionuclide Conjugates → Antibody Conjugates → Antibody-Based Therapeutics, Beta-minus Emitters → Radiopharmaceuticals, Gamma Emitters → Radiopharmaceuticals, Antibody Fragments → Engineered Antibody Formats → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
177Lu-A2DM is an investigational, preclinical targeted radiopharmaceutical (radionuclide drug conjugate) developed by the City of Hope National Medical Center for the treatment of prostate stem cell antigen (PSCA)-expressing malignancies, such as pancreatic ductal adenocarcinoma (PDAC). The agent consists of an engineered humanized antibody fragment (A2 scFv-Fc2 double mutant, or A2DM) that specifically targets PSCA, conjugated to the chelator p-SCN-Bn-CHX-A''-DTPA and radiolabeled with the beta-emitting radionuclide lutetium-177 (177Lu). The A2DM fragment features a double mutation in the FcRn binding site designed to accelerate blood clearance and reduce bone marrow and kidney radiotoxicity, thereby improving the therapeutic index. In preclinical syngeneic mouse models of pancreatic cancer, 177Lu-A2DM has demonstrated dose-dependent tumor growth inhibition and improved median survival with minimal toxicity.
- Other names
- 177Lu-A2 scFv-Fc2DM177Lu-labeled A2DMA2DMA-2DMA 2DMlutetium Lu 177-A2DM
02
Targets
PSCA (Prostate stem cell antigen)
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