Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-1-19
pubmed:abstractText
Tumor-associated antigens (TAA) are typically poorly immunogenic "self" antigens. An effective strategy to break tolerance and induce antitumor immunity is by genetic vaccination, employing the orthologous TAA-sequence from a different species. We recently developed a clinically relevant approach for intravascular hydrodynamic limb vein (HLV) delivery of nucleic acids to skeletal muscle. Using the human gp100 xenogeneic TAA in the murine B16 melanoma model, we show that genetic vaccination of mice by HLV plasmid DNA delivery was highly effective at breaking tolerance against the homologous murine gp100 (mgp100) TAA and induced prophylactic antitumor protection. HLV vaccination resulted in an anti-hgp100 humoral and cellular response, with 4-5% of CD8(+) T cells being gp100(25-33)-epitope-specific. Vaccinated animals demonstrated in vivo cytolytic activity against human and mgp100(25-33) peptide-pulsed targets. Antitumor immunity could be adoptively transferred by splenocytes from human gp100-vaccinated animals. Furthermore, a durable antitumor memory response was established as approximately 3% of CD8(+) T cells were gp100(25-33) antigen-specific in mice 6 months after vaccination. Following a single HLV human gp100 DNA boost, this level increased to approximately 17% and protected animals from subsequent B16 tumor rechallenge. Our results warrant further consideration of HLV as a clinically relevant method for cancer gene therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1525-0016
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
422-30
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17235322-Animals, pubmed-meshheading:17235322-Antigens, Neoplasm, pubmed-meshheading:17235322-Blotting, Western, pubmed-meshheading:17235322-CD8-Positive T-Lymphocytes, pubmed-meshheading:17235322-COS Cells, pubmed-meshheading:17235322-Cancer Vaccines, pubmed-meshheading:17235322-Cell Line, Tumor, pubmed-meshheading:17235322-Cercopithecus aethiops, pubmed-meshheading:17235322-Epitopes, T-Lymphocyte, pubmed-meshheading:17235322-Female, pubmed-meshheading:17235322-Flow Cytometry, pubmed-meshheading:17235322-Hindlimb, pubmed-meshheading:17235322-Humans, pubmed-meshheading:17235322-Injections, Intravenous, pubmed-meshheading:17235322-Melanoma, Experimental, pubmed-meshheading:17235322-Membrane Glycoproteins, pubmed-meshheading:17235322-Mice, pubmed-meshheading:17235322-Mice, Inbred C57BL, pubmed-meshheading:17235322-Vaccination, pubmed-meshheading:17235322-Vaccines, DNA, pubmed-meshheading:17235322-gp100 Melanoma Antigen
pubmed:year
2007
pubmed:articleTitle
Hydrodynamic limb vein delivery of a xenogeneic DNA cancer vaccine effectively induces antitumor immunity.
pubmed:affiliation
Mirus Bio Corporation, Madison, Wisconsin 53719, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural