177Lu-labeled single-domain antibody (anti-CAF)

177Lu-labeled single-domain antibody (anti-CAF), also known as CAM-FAP-Lu-177 or [177Lu]Lu-DOTA-4AH29, is a preclinical-stage targeted radiopharmaceutical being developed by Precirix in collaboration with the Institut de Recherche en Cancérologie de Montpellier (IRCM) and Vrije Universiteit Brussel (VUB). It consists of a camelid single-domain antibody (sdAb), designated 4AH29, that specifically targets fibroblast activation protein alpha (FAP-α) overexpressed on cancer-associated fibroblasts (CAFs) in the tumor microenvironment, conjugated to the beta-emitting radionuclide Lutetium-177 (177Lu) via a DOTA chelator. The drug is designed for targeted radionuclide therapy (TRT) of FAP-expressing solid tumors, such as pancreatic ductal adenocarcinoma (PDAC). Preclinical studies have demonstrated that targeting CAFs with this radiopharmaceutical can induce tumor growth regression and bystander cytotoxic effects on neighboring cancer cells without inducing a senescence-associated secretory phenotype (SASP), offering a promising therapeutic index, particularly when combined with pretargeting strategies to mitigate renal retention.

Other names

177Lu-DOTA-4AH29177Lu-labeled anti-FAP sdAb177Lu-labeled anti-FAP single-domain antibody177Lu-labeled single-domain antibody (anti-CAF)177Lu-labeled single-domain antibody (anti-FAP)[177Lu]Lu-DOTA-4AH29