Document Detail


Immunogene therapy for murine melanoma using recombinant adenoviral vectors expressing melanoma-associated antigens.
MedLine Citation:
PMID:  10933943     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adenoviral vectors expressing tumor-associated antigens can be used to evoke a specific immune response and inhibit tumor growth. In this study, we tested the efficacy of adenoviral vectors encoding human gp100 (Ad2/hugp100), murine gp100 (Ad2/mugp100), or murine TRP-2 (Ad2/muTRP-2) for their ability to elicit a specific cellular immune response and inhibit the growth of B16 melanoma tumor cells in the mouse. C57BL/6 mice were immunized with Ad2/hugp100, Ad2/mugp100, or Ad2/muTRP-2 either 2 weeks prior to B16-F10 tumor challenge (prophylactic treatment) or 3 days after tumor challenge (active treatment). Ad2/hugp100 and Ad2/muTRP-2 administered to two or more intradermal (i.d.) sites inhibited subsequent subcutaneous tumor growth in > or = 80% of the mice and elicited an antigen-specific cytotoxic T lymphocyte response, whereas other administration routes were not as effective. Ad2/mugp100 administered to two i.d. sites did not inhibit tumor growth or provoke cellular immunity. Immunization was less effective with active treatment where tumor growth was not significantly inhibited by a single dose of either Ad2/muTRP-2 or Ad2/hugp100. However, increasing the number of intradermal immunization sites and the number of doses resulted in progressive improvements in protection from tumor growth in the active treatment model. In conclusion, breaking host tolerance to elicit protective immunity by using adenoviral vectors expressing melanoma-associated antigens is dependent upon the choice of antigen, the site of administration, and the number of doses. These observations provide insights into the clinical applicability of adenoviral vaccines for immunotherapy of malignant diseases.
Authors:
M A Perricone; K A Claussen; K A Smith; J M Kaplan; S Piraino; S Shankara; B L Roberts
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Molecular therapy : the journal of the American Society of Gene Therapy     Volume:  1     ISSN:  1525-0016     ISO Abbreviation:  Mol. Ther.     Publication Date:  2000 Mar 
Date Detail:
Created Date:  2000-09-01     Completed Date:  2000-09-01     Revised Date:  2012-03-02    
Medline Journal Info:
Nlm Unique ID:  100890581     Medline TA:  Mol Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  275-84     Citation Subset:  IM    
Affiliation:
Genzyme Molecular Oncology, Framingham, Massachusetts 01701-9322, USA. michael.perricone@genzyme.com
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*,  immunology
Animals
Antigens, Neoplasm / genetics,  metabolism*
Gene Therapy*
Genetic Vectors / administration & dosage
Humans
Immunization
Immunotherapy
Injections
Intramolecular Oxidoreductases / genetics,  metabolism*
Melanoma / immunology,  prevention & control,  therapy*
Membrane Glycoproteins / genetics,  metabolism*
Mice
Mice, Inbred C57BL
Neoplasm Proteins / genetics,  metabolism*
Neoplasm Transplantation
Tumor Cells, Cultured
gp100 Melanoma Antigen
Chemical
Reg. No./Substance:
0/Antigens, Neoplasm; 0/Membrane Glycoproteins; 0/Neoplasm Proteins; 0/PMEL protein, human; 0/Si protein, mouse; 0/gp100 Melanoma Antigen; EC 5.3.-/Intramolecular Oxidoreductases; EC 5.3.3.12/dopachrome isomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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