In vivo gene therapy of malignant tumours with heat shock protein-65 gene.
We have previously shown that ex vivo insertion of a gene encoding the mycobacterial heat shock protein-65 into tumour cells results in their inability to form tumours in mice. We report regression of highly malignant reticulum cell sarcomas (J774) after liposome-mediated gene transfer in vivo. Heat shock gene transfer resulted in tumour regression both in immunocompetent and immunodeficient SCID mice. Complete tumour eradication, however, was detected only in immunocompetent animals, confirming the role of T cells in tumour rejection. Treatment of tumour bearing mice with the heat shock gene-liposome complex resulted in the production of antibodies against the tumour cells, indicating an increase in the antigenicity of the tumour after gene transfer. These results suggest that the heat shock protein-65 gene could provide a novel approach for the treatment of established tumours.
Lukacs
K V
KV
Division of Mycobacterial Research, National Institute for Medical Research, London, UK.
Nakakes
A
A
Atkins
C J
CJ
Lowrie
D B
DB
Colston
M J
MJ
D000818:Animals; D000912:Antibodies, Neoplasm / Q000096:biosynthesis; D001426:Bacterial Proteins; D018834:Chaperonin 60; D018833:Chaperonins / Q000235:genetics*; D005260:Female; D018014:Gene Transfer Techniques; D005798:Genes, Bacterial; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009161:Mycobacterium / Q000235:genetics; D009374:Neoplasms, Experimental / Q000276:immunology / Q000628:therapy*
D000912:Antibodies, Neoplasm; D001426:Bacterial Proteins; D018834:Chaperonin 60; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins