TRANSDUCTION OF NONSMALL CELL LUNG-CANCER CELLS BY ADENOVIRAL AND RETROVIRAL VECTORS

Gene transfer into a panel of non-small cell lung cancer (NSCLC) cells by adenoviral (Ad) and retroviral (RV) vectors was studied, indexed t o multiplicity of infection (MOI), Ad vectors transduce squamous, aden osquamous, and malignant mesothelioma cells with greater efficiency th an large cells or adenocarcinoma cells. Transduction-sensitive cells b ind the Ad vector with specificity for the Ad fiber knob, and internal ize vector efficiently. Transduction-refractory cells bind and interna lize vector by less efficient pathways. Like Ad vectors, there is hete rogeneity in RV transduction efficiencies of different NSCLC subtypes. with respect to the most common cell type metastatic to the pleural s pace (adenocarcinoma), amphotropic retroviral vectors transduce cells of this subtype more efficiently (at a lower MOI) than Ad, RV transduc tion is not solely dependent on cellular replication, and both permiss ive and refractory cell lines express the mRNA for the amphotropic RV receptor. These observations suggest that neither Ad nor RV vectors wi ll suffice a priori as the optimal gene transfer vehicle, and successf ul gene therapy of lung cancer may require tumor-specific or patient-s pecific vectors.