Calu-3 is a human lung cancer cell line commonly used in cancer research and drug development. Calu-3 cells are epithelial and can act as respiratory models in preclinical applications. Calu-3 cells were first derived in 1975 by Germain Trempe and Jorgen Fogh of the Memorial Sloan Kettering Cancer Center. The cells were isolated from the pleural effusion of a 25-year-old Caucasian male with lung adenocarcinoma.

Calu-3 is a non-small-cell lung cancer cell line that grows in adherent culture and displays epithelial morphology. These cells have constitutively active ErbB2/Her2 genes due to the amplification of the ERBB2 gene. They express wild-type EGFR and mutant K-Ras (G13D). In addition, they harbor mutations in TP53 and CDKN2A genes. The Calu-3 cells are sensitive to erlotinib (EGFR tyrosine kinase inhibitor) and cetuximab (a monoclonal antibody that blocks ligand binding to EGFR and prevents downstream signaling), two commonly used drugs targeting ErbB receptors. These cells are capable of forming tumors in immunocompromised mice.

Calu-3 cells are commonly used as both in vivo and in vitro models for drug development against lung cancer. The cells have been used in studies of pulmonary drug delivery, demonstrating a capacity to intake low molecular weight substances. Calu-3 cells have served as respiratory models for air intake and lung injury due to their responsiveness to foreign substances. The Calu-3 cell line has shown to be useful in the study of chloride ion secretion by lung epithelial cells.