PMID- 10724038
OWN - NLM
STAT- MEDLINE
DCOM- 20000413
LR  - 20061115
IS  - 1043-0342 (Print)
IS  - 1043-0342 (Linking)
VI  - 11
IP  - 4
DP  - 2000 Mar 1
TI  - Highly efficient transduction and expression of cytokine genes in human tumor 
      cells by means of autonomous parvovirus vectors; generation of antitumor 
      responses in recipient mice.
PG  - 597-609
AB  - The possible use of recombinant autonomous parvoviruses as vectors to efficiently 
      express therapeutic cytokines in human tumor cells was evaluated in vitro and in 
      vivo. The parvovirus H1 was used to generate recombinant viruses (rH1) that 
      carried transgenes encoding either human interleukin 2 (IL-2) or monocyte 
      chemotactic protein 1 (MCP-1), in replacement of part of the capsid genes. Such 
      rH11 viruses have been shown to retain in vitro the intrinsic oncotropic 
      properties of the parental virus. On infection with the recombinant viruses at an 
      input multiplicity of 1 replication unit (RU) per cell, HeLa cultures were 
      induced to release 4-10 microg of cytokine per 10(6) cells over a period of 5 
      days. The expression of the rH1-transduced human cytokine/chemokine could also be 
      detected in tumor material recovered from nude mice that had been subcutaneously 
      engrafted with in vitro-infected HeLa cells. The formation of tumors from HeLa 
      xenografts was reduced by 90% compared with wild-type or mock-infected cells as a 
      result of cells preinfected with IL2-expressing virus at an input multiplicity as 
      low as 1 RU per cell. Tumors arising from HeLa cells infected with transgene-free 
      or MCP1-expressing vectors or with wild-type H1 virus were not rejected at this 
      virus dose. Tumors infected with rH1/IL-2 virus displayed markers indicative of 
      their infiltration with NK cells in which the cytocidal program was activated, 
      whereas little NK activity was detected in wild-type virus or mock-infected 
      tumors. Altogether, these data show that the IL-2 expressing H1 vector was a more 
      potent antineoplastic agent than the parental virus, and point to the possible 
      application of recombinant autonomous parvoviruses toward therapy of some human 
      tumors.
FAU - Haag, A
AU  - Haag A
AD  - Applied Tumor Virology Abteilung F0100 and INSERM U375 Deutsches 
      Krebsforschungszentrum, Heidelberg, Germany.
FAU - Menten, P
AU  - Menten P
FAU - Van Damme, J
AU  - Van Damme J
FAU - Dinsart, C
AU  - Dinsart C
FAU - Rommelaere, J
AU  - Rommelaere J
FAU - Cornelis, J J
AU  - Cornelis JJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Cytokines)
RN  - 0 (DNA Primers)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Cytokines/*genetics
MH  - Cytotoxicity, Immunologic/genetics
MH  - DNA Primers
MH  - Female
MH  - *Gene Expression Regulation
MH  - *Genetic Vectors
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasms, Experimental/immunology/*prevention & control
MH  - Parvovirus/*genetics
MH  - Recombination, Genetic
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - *Transduction, Genetic
MH  - Transgenes
MH  - Viral Nonstructural Proteins/genetics
EDAT- 2000/03/21 09:00
MHDA- 2000/04/15 09:00
CRDT- 2000/03/21 09:00
PHST- 2000/03/21 09:00 [pubmed]
PHST- 2000/04/15 09:00 [medline]
PHST- 2000/03/21 09:00 [entrez]
AID - 10.1089/10430340050015789 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2000 Mar 1;11(4):597-609. doi: 10.1089/10430340050015789.