Kay M A, Holterman A X, Meuse L, Gown A, Ochs H D, Linsley P S, Wilson C B
Department of Medicine, University of Washington, Seattle 98195, USA.
Nat Genet. 1995 Oct;11(2):191-7. doi: 10.1038/ng1095-191.
Recombinant adenovirus vectors are efficient at transferring genes into somatic tissues but are limited for use in clinical gene therapy by immunologic factors that result in the rapid loss of gene expression and inhibit secondary gene transfer. This study demonstrates that systemic coadministration of recombinant adenovirus with soluble CTLA4Ig, which is known to block co-stimulatory signals between T cells and antigen presenting cells, leads to persistent adenoviral gene expression in mice without long-term immunosuppression. This form of immunotherapy greatly enhances the likelihood that recombinant adenovirus vectors will be useful for human gene therapy.
重组腺病毒载体在将基因转移到体细胞组织方面效率很高,但由于免疫因素限制了其在临床基因治疗中的应用,这些免疫因素会导致基因表达迅速丧失并抑制二次基因转移。本研究表明,将重组腺病毒与可溶性CTLA4Ig进行全身联合给药,已知可溶性CTLA4Ig可阻断T细胞与抗原呈递细胞之间的共刺激信号,可使小鼠体内腺病毒基因持续表达,而无需长期免疫抑制。这种免疫治疗形式大大提高了重组腺病毒载体用于人类基因治疗的可能性。