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Development of antibody-drug conjugates targeting L1CAM to treat metastatic cancer

Park JS, Kenum C, He L, Khan AG, Pohl MA, White TE, Kodangattil SR, Rudin CM, Balderes PJ, Lorenz IC, Massagué J, anesh K (2025) Development of antibody-drug conjugates targeting L1CAM to treat metastatic cancer. bioRxiv 2025.10.01.679843. doi: 10.1101/2025.10.01.679843

Objective: To develop L1CAM-targeted antibody-drug conjugates (ADCs) using high-affinity monoclonal antibodies and assess their therapeutic potential against metastatic cancer.

Summary: L1CAM ADCs conjugated with the potent payload PNU-159682 achieved strong cytotoxicity, tumor regression, and prolonged survival in models of metastatic breast and lung cancer. Safety studies indicated a favorable therapeutic window for clinical translation.

Usage: FabFc-ZAP Human (IT-65) was used to evaluate antibody internalization. FabFc-ZAP was incubated with L1CAM candidate antibodies or isotype control and applied to L1CAM-HEK293T cells, with viability measured after five days.

Related Products: FabFc-ZAP human (Cat. #IT-65)

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