NONDEPLETING ANTI-CD4 ANTIBODY TREATMENT PROLONGS LUNG-DIRECTED E1-DELETED ADENOVIRUS-MEDIATED GENE-EXPRESSION IN RATS

E1-deleted adenoviral vectors are efficient vectors for somatic cell g ene therapy, but transgene expression is limited in part by a cytotoxi c T cell response directed against virally transduced cells, Moreover, the development of a neutralizing antibody response limits secondary gene transfer with these vectors, Therapy with a depleting anti-CD4 an tibody permits prolonged transgene expression in the lung and liver of mice, Furthermore, transient depletion of CD4(+) lymphocytes blocks n eutralizing antibody production and therefore allows repeat administra tion and expression of E1-deleted recombinant adenovirus, In this stud y, we investigated the efficacy of a novel nondepleting anti-CD4 antib ody (RIB 5/2) in a model of lung-directed gene therapy in outbred rats , Treatment with RIB 5/2 permitted prolonged reporter gene expression and reduced adenovirus-induced peribronchial and alveolar inflammation in the lung, Moreover administration of RIB 5/2 blocked the developme nt of an anti-adenoviral neutralizing antibody response in the lung an d permitted secondary administration and expression of a recombinant a denovirus. These data support the role of immunomodulation in prolongi ng in vivo transgene expression by recombinant adenovirus.