Adenovirus/alphavirus hybrid vector for the effective administration and expression of therapeutic genes in tumour cells

摘要

#$%^&*AU2010214637B220120426.pdf#####ABSTRACT ADENOVIRUS/ALPHAVIRUS HYBRID VECTOR FOR THE EFFECTIVE ADMINISTRATION AND EXPRESSION OF THERAPEUTIC GENES IN TUMOUR 5 CELLS The present invention relates to a genic expression adenoviral hybrid vector characterized in that it contains at least the following elements, oriented in the direction 5' to 10 3': i. a first chain of adenoviral origin comprising a first inverted terminal repeat (ITR) sequence and a signal sequence for packaging of the adenovirus; ii. a first non-encoding stuffer sequence; iii. a sequence corresponding to a tissue specific promoter; iv. a chain of cDNA derived from an 15 alphavirus, the sequence of which is partly complementary to an alphaviral RNA sequence, comprising at least a sequence encoding for at least one exogenous gene of interest; v. a polyadenylation sequence; and vi. a second adenoviral inverted terminal repeat (ITR) sequence, it preferably relates to an 20 adenoviral hybrid vector comprising as exogenous gene of interest the therapeutic gene of mammalian interleukin IL-12 and even more preferably human interleukin hIL-12; and to the use of the hybrid vector in a process for transferring genetic material tc a cell, particularly a tumor cell that preferably 25 expresses alpha-fetoprotein (AFP), and to its use for inducing an immune response against foreign antigens. 301 / 17 A ITR HPIRT AFP (pte) Rep nl- IpoliA C346 ITR L.- SFV replicon B NON HCC CELLS HCC CELLS oIL-12 There is not SFV replicon transcription Apoptoss Im + antigen Inmunocytes APCs Anti-tumor immunity Figure 1 v Pr. sg AFP(p+e) SFV nspl-4 LacZ PoliA AFP-SFV-LacZ AFP-LacZ AFP(p+e) LacZ PoliA AF-F-l-2AFP(p+e) SFV nspl-4 mIL-12 PoiA AFP-SFV-mIL-1 2 AFP-mlL-12 AFP(p+e) mIL-12 PoliA Figure 2