PMID- 1423266
OWN - NLM
STAT- MEDLINE
DCOM- 19921209
LR  - 20220225
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 52
IP  - 22
DP  - 1992 Nov 15
TI  - Retroviral vector-mediated lymphokine gene transfer into human renal cancer 
      cells.
PG  - 6229-36
AB  - Effective vaccination against cancer, either for prophylaxis or therapy, has been 
      an elusive goal for years. Cytokine gene therapy offers a novel approach to 
      generate immunogenic tumor cell vaccines. To examine the feasibility of cytokine 
      gene transfer into human renal cancer (RC) cells, we introduced the cDNAs for 
      human interleukin-2 (IL-2) or interferon-gamma (IFN-gamma) into various RC cell 
      lines with retroviral vectors. Using the NIH3T3 amplification assay, no 
      replication competent retroviral particles were detectable in cell culture 
      supernatants taken from gene-modified RC cell lines. Efficient expression of both 
      lymphokines was achieved. Depending on the cell line and the vector construct 
      used, lymphokine gene-modified human RC cell lines released 4 to 29 units/10(6) 
      cells of IL-2, or up to 10 units/10(6) cells of IFN-gamma within 48 h. 
      Fluorescence-activated cell sorter analysis of SK-RC-29 cells releasing IFN-gamma 
      showed increased expression of major histocompatibility complex class I antigen, 
      beta 2-microglobulin, and ICAM-1, as well as induction of major 
      histocompatibility complex class II antigen expression [human leukocyte 
      antigen(HLA)-DR, -DP], but no changes in these cell surface markers were observed 
      with SK-RC-29 cells releasing IL-2. Following in vitro gamma-irradiation with 
      5,000 or 10,000 rad, growth of lymphokine gene-modified RC cells was abrogated, 
      but their capability to release lymphokine and express lymphokine-induced 
      antigenic determinants, such as HLA-DR, was retained. Tumor formation by the 
      human RC cell line SK-RC-29 in BALB/c nude mice was not affected by IFN-gamma 
      secretion, but was inhibited by in vivo release of IL-2 from s.c. injected tumor 
      cells. These studies demonstrate the feasibility of retroviral mediated 
      lymphokine-gene transfer into human RC cells and suggest a means for generating 
      autologous or HLA-matched allogeneic tumor cell vaccines for the treatment of 
      patients with renal cell carcinoma.
FAU - Gastl, G
AU  - Gastl G
AD  - Department of Surgery/Urology, New York Hospital-Cornell Medical Center, New 
      York.
FAU - Finstad, C L
AU  - Finstad CL
FAU - Guarini, A
AU  - Guarini A
FAU - Bosl, G
AU  - Bosl G
FAU - Gilboa, E
AU  - Gilboa E
FAU - Bander, N H
AU  - Bander NH
FAU - Gansbacher, B
AU  - Gansbacher B
LA  - eng
GR  - CA-08748/CA/NCI NIH HHS/United States
GR  - CA-33049/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Interleukin-2)
RN  - 0 (Lymphokines)
RN  - 82115-62-6 (Interferon-gamma)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Antigens, Neoplasm/analysis
MH  - Carcinoma, Renal Cell/*genetics/microbiology/physiopathology
MH  - Cell Survival/radiation effects
MH  - DNA/genetics
MH  - Dose-Response Relationship, Radiation
MH  - Gamma Rays
MH  - Gene Expression/genetics
MH  - Genetic Vectors/genetics
MH  - Humans
MH  - Interferon-gamma/biosynthesis/genetics/metabolism
MH  - Interleukin-2/biosynthesis/genetics/metabolism
MH  - Kidney Neoplasms/*genetics/microbiology/physiopathology
MH  - Lymphokines/biosynthesis/*genetics/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Phenotype
MH  - Retroviridae/*genetics/physiology
MH  - Transfection
MH  - Transplantation, Heterologous
MH  - Tumor Cells, Cultured
MH  - Virus Replication/physiology
EDAT- 1992/11/15 00:00
MHDA- 1992/11/15 00:01
CRDT- 1992/11/15 00:00
PHST- 1992/11/15 00:00 [pubmed]
PHST- 1992/11/15 00:01 [medline]
PHST- 1992/11/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1992 Nov 15;52(22):6229-36.