DNA vaccines encoding full-length or truncated Neu induce protective immunity against Neu-expressing mammary tumors.
We generated DNA expression vectors encoding the full-length neu cDNA (designated pNeuN), the neu extracellular domain (pNeuE), or the neu extracellular and transmembrane domains (pNeuTM). The 293 cells transfected with pNeuN or pNeuTM expressed the neu extracellular domain on the surface membrane, whereas 293 cells transfected with pNeuE secreted the extracellular domain of neu into the culture supernatant. We examined whether i.m. injection of either of these plasmids could induce protective immunity in FVB/N mice against the adoptive transfer of Tgl-1 cells, a neu-expressing tumor cell line generated from a mouse mammary tumor that spontaneously arose in a FVB/N neu-transgenic mouse. The i.m. injection of pNeuTM or pNeuE, and to a lesser extent pNeuN, induced protective immunity against a subsequent challenge with Tgl-1 cells in FVB/N mice. In addition, the coinjection of a plasmid encoding interleukin-2 (designated pIL-2) augmented the efficacy of each of the pNeu plasmids for inducing protective immunity. The plasmid pNeuTM seemed to be the most effective for inducing anti-neu antibodies. However, the generation of detectable anti-neu antibodies in response to any one of these pNeu plasmids was not enhanced by coinjection of pIL-2 and was not required for protective immunity against Tgl-1 cells. These studies demonstrate that DNA expression vectors encoding soluble or membrane-bound forms of neu lacking the cytoplasmic kinase domain can be effective in inducing protective antitumor immunity.
Chen
Y
Y
University of California at San Diego Human Gene Therapy Program, Department of Medicine, University of California at San Diego School of Medicine, La Jolla 92093-0663, USA.
Hu
D
D
Eling
D J
DJ
Robbins
J
J
Kipps
T J
TJ
D019264:Adoptive Transfer; D000818:Animals; D017931:DNA Primers / Q000737:chemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018734:Genes, erbB-2 / Q000235:genetics*; D007109:Immunity; D015151:Immunoblotting; D007273:Injections, Intramuscular; D007376:Interleukin-2 / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010957:Plasmids / Q000235:genetics; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics
D017931:DNA Primers; D007376:Interleukin-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D019444:Vaccines, DNA