PubMed:15788693 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/15788693","sourcedb":"PubMed","sourceid":"15788693","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/15788693","text":"Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses.\nPURPOSE: Cancer vaccines targeting tumor-associated antigens are being investigated for the therapy of tumors. Numerous strategies, including the direct intratumoral (i.t.) vaccination route, have been examined. For tumors expressing carcinoembryonic antigen (CEA) as a model tumor-associated antigen, we previously designed poxviral vectors that contain the transgenes for CEA and a triad of T-cell costimulatory molecules, B7-1, intercellular adhesion molecule-1, (ICAM-1), and leukocyte function associated antigen-3 (LFA-3) (CEA/TRICOM). Two types of poxvirus vectors were developed: replication-competent recombinant vaccinia and replication-defective recombinant fowlpox. We have shown previously that a vaccine regimen composed of priming mice s.c. with recombinant vaccinia-CEA/TRICOM and boosting i.t. with recombinant fowlpox-CEA/TRICOM was superior to priming and boosting vaccinations using the conventional s.c. route in inducing T-cell responses specific for CEA. These studies also showed that CEA was needed to be present both in the vaccine and in the tumor for therapeutic effects.\nEXPERIMENTAL DESIGN: To determine specific immune responses associated with vaccination-mediated tumor regression, CEA-transgenic mice bearing CEA(+) tumors were vaccinated with the CEA/TRICOM s.c./i.t. regimen, and T-cell immune responses were assessed.\nRESULTS: In CEA(+) tumor-bearing mice vaccinated with the CEA/TRICOM s.c./i.t. regimen, T-cell responses could be detected not only to CEA encoded in vaccine vectors but also to other antigens expressed on the tumor itself: wild-type p53 and an endogenous retroviral epitope of gp70. Moreover, the magnitude of CD8(+) T-cell immune responses to gp70 was far greater than that induced to CEA or p53. Finally, the predominant T-cell population infiltrating the regressing CEA(+) tumor after therapy was specific for gp70.\nCONCLUSION: These studies show that the breadth and magnitude of antitumor immune cascades to multiple antigens could be critical in the therapy of established tumors.","tracks":[{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":1098,"end":1101},"obj":"gene:1048"},{"id":"T1","span":{"begin":953,"end":960},"obj":"disease:C0016629"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"attributes":[{"subj":"T0","pred":"source","obj":"DisGeNET"},{"subj":"T1","pred":"source","obj":"DisGeNET"}]},{"project":"DisGeNET5_gene_disease","denotations":[{"id":"15788693-5#104#107#gene1048","span":{"begin":907,"end":910},"obj":"gene1048"},{"id":"15788693-5#158#161#gene1048","span":{"begin":961,"end":964},"obj":"gene1048"},{"id":"15788693-5#295#298#gene1048","span":{"begin":1098,"end":1101},"obj":"gene1048"},{"id":"15788693-5#150#157#diseaseC0016629","span":{"begin":953,"end":960},"obj":"diseaseC0016629"}],"relations":[{"id":"104#107#gene1048150#157#diseaseC0016629","pred":"associated_with","subj":"15788693-5#104#107#gene1048","obj":"15788693-5#150#157#diseaseC0016629"},{"id":"158#161#gene1048150#157#diseaseC0016629","pred":"associated_with","subj":"15788693-5#158#161#gene1048","obj":"15788693-5#150#157#diseaseC0016629"},{"id":"295#298#gene1048150#157#diseaseC0016629","pred":"associated_with","subj":"15788693-5#295#298#gene1048","obj":"15788693-5#150#157#diseaseC0016629"}],"attributes":[{"subj":"15788693-5#104#107#gene1048","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15788693-5#158#161#gene1048","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15788693-5#295#298#gene1048","pred":"source","obj":"DisGeNET5_gene_disease"},{"subj":"15788693-5#150#157#diseaseC0016629","pred":"source","obj":"DisGeNET5_gene_disease"}]},{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":134,"end":1224},"obj":"OBJECTIVE"},{"id":"T2","span":{"begin":1246,"end":1479},"obj":"METHODS"},{"id":"T3","span":{"begin":1489,"end":1999},"obj":"RESULTS"},{"id":"T4","span":{"begin":2012,"end":2167},"obj":"CONCLUSIONS"}],"attributes":[{"subj":"T1","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T2","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T3","pred":"source","obj":"PubMed_Structured_Abstracts"},{"subj":"T4","pred":"source","obj":"PubMed_Structured_Abstracts"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"DisGeNET","color":"#ecd493","default":true},{"id":"DisGeNET5_gene_disease","color":"#ba93ec"},{"id":"PubMed_Structured_Abstracts","color":"#93eca0"}]}]}}