PMID- 9597569
OWN - NLM
STAT- MEDLINE
DCOM- 19980804
LR  - 20121115
IS  - 1061-6128 (Print)
IS  - 1061-6128 (Linking)
VI  - 7
IP  - 2
DP  - 1998 Apr
TI  - Antileukemic activity of TNF-alpha gene therapy with myeloid progenitor cells 
      against minimal leukemia.
PG  - 115-25
AB  - Tumor necrosis factor-alpha (TNF-alpha) has exhibited antitumor activity against 
      a variety of tumors in rodents and human tumor xenografts in nude mice, but it 
      has been only marginally effective in cancer patients because of dose-limiting 
      toxicity associated with systemic TNF-alpha therapy. To circumvent toxicity and 
      to test the antileukemic activity against quantitated minimal leukemia, we have 
      cloned human TNF-alpha (HuTNF-alpha) gene in an advanced myeloid progenitor cell 
      line. 32Dcl3 myeloid progenitor cells transfected with HuTNF-alpha cDNA by the 
      retroviral supernatant infection method stably express HuTNF-alpha gene and 
      secrete substantial amounts of HuTNF-alpha. When injected i.v. into irradiated 
      mice, transduced cells could be detected in the marrow but not in spleen or liver 
      10-12 days later. Injection of 5 x 10(6) transduced cells produced no obvious 
      symptoms of TNF-alpha toxicity (i.e., weight loss, cachexia, or fever) suggesting 
      that TNF-alpha producing cells are well tolerated by the recipient mice. 
      Coinjection of 5 x 10(6) transduced cells and 10(2) or 10(3) 32Dp210 leukemia 
      (BCR/ABL+) cells resulted in inhibition of leukemia development by 10(2) but not 
      10(3) 32Dp210 cells. An equal dose of nontransduced 32Dcl3 cells was ineffective 
      in inhibiting leukemia progression by 10(2) 32Dp210 cells. Mice that rejected 
      leukemia were BCR/ABL oncogene negative 8 weeks after leukemia cell injection. 
      These data demonstrate the potential for TNF-alpha gene therapy for destroying 
      residual leukemia, without the toxicity of systemic TNF-alpha therapy, following 
      cytoreductive therapy and bone marrow transplant.
FAU - Gautam, S C
AU  - Gautam SC
AD  - Division of Hematology/Oncology, Henry Ford Hospital, Detroit, MI 48202, USA.
FAU - Pindolia, K R
AU  - Pindolia KR
FAU - Xu, Y X
AU  - Xu YX
FAU - Janakiraman, N
AU  - Janakiraman N
FAU - Chapman, R A
AU  - Chapman RA
FAU - Freytag, S O
AU  - Freytag SO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Hematother
JT  - Journal of hematotherapy
JID - 9306048
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Line
MH  - Disease Models, Animal
MH  - Gene Expression
MH  - Genetic Therapy/*methods
MH  - *Hematopoietic Stem Cells
MH  - Humans
MH  - Leukemia, Experimental/*therapy
MH  - Mice
MH  - Mice, Inbred C3H
MH  - Tissue Distribution
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 1998/05/23 00:00
MHDA- 1998/05/23 00:01
CRDT- 1998/05/23 00:00
PHST- 1998/05/23 00:00 [pubmed]
PHST- 1998/05/23 00:01 [medline]
PHST- 1998/05/23 00:00 [entrez]
AID - 10.1089/scd.1.1998.7.115 [doi]
PST - ppublish
SO  - J Hematother. 1998 Apr;7(2):115-25. doi: 10.1089/scd.1.1998.7.115.