Matches in SemOpenAlex for { <https://semopenalex.org/work/W4361943852> ?p ?o ?g. }
Showing items 1 to 94 of
94
with 100 items per page.
- W4361943852 abstract "<div>Abstract<p><b>Purpose:</b> Overexpression of the breast cancer oncogene <i>HER2</i> correlates with poor survival. Current <i>HER2</i>-directed therapies confer limited clinical benefits and most patients experience progressive disease. Because refractory tumors remain strongly <i>HER2</i>+, vaccine approaches targeting <i>HER2</i> have therapeutic potential, but wild type (wt) <i>HER2</i> cannot safely be delivered in imunogenic viral vectors because it is a potent oncogene. We designed and tested several HER2 vaccines devoid of oncogenic activity to develop a safe vaccine for clinical use.</p><p><b>Experimental Design:</b> We created recombinant adenoviral vectors expressing the extracellular domain of HER2 (Ad-HER2-ECD), ECD plus the transmembrane domain (Ad-HER2-ECD-TM), and full-length HER2 inactivated for kinase function (Ad-HER2-ki), and determined their immunogenicity and antitumor effect in wild type (WT) and HER2-tolerant mice. To assess their safety, we compared their effect on the cellular transcriptome, cell proliferation, anchorage-dependent growth, and transformation potential <i>in vivo</i>.</p><p><b>Results:</b> Ad-HER2-ki was the most immunogenic vector in WT animals, retained immunogenicity in HER2-transgenic tolerant animals, and showed strong therapeutic efficacy in treatment models. Despite being highly expressed, HER2-ki protein was not phosphorylated and did not produce an oncogenic gene signature in primary human cells. Moreover, in contrast to HER2-wt, cells overexpressing HER2-ki were less proliferative, displayed less anchorage-independent growth, and were not transformed <i>in vivo</i>.</p><p><b>Conclusions:</b> Vaccination with mutationally inactivated, nononcogenic Ad-HER2-ki results in robust polyclonal immune responses to HER2 in tolerant models, which translates into strong and effective antitumor responses <i>in vivo</i>. Ad-HER2-ki is thus a safe and promising vaccine for evaluation in clinical trials. Clin Cancer Res; 16(5); 1466–77</p></div>" @default.
- W4361943852 created "2023-04-05" @default.
- W4361943852 creator A5000371531 @default.
- W4361943852 creator A5008662619 @default.
- W4361943852 creator A5011368708 @default.
- W4361943852 creator A5019037704 @default.
- W4361943852 creator A5020602283 @default.
- W4361943852 creator A5022822590 @default.
- W4361943852 creator A5028156079 @default.
- W4361943852 creator A5044565308 @default.
- W4361943852 creator A5045134210 @default.
- W4361943852 creator A5053154937 @default.
- W4361943852 creator A5054445393 @default.
- W4361943852 creator A5055582773 @default.
- W4361943852 creator A5060398911 @default.
- W4361943852 creator A5075662505 @default.
- W4361943852 creator A5077597600 @default.
- W4361943852 creator A5083266436 @default.
- W4361943852 creator A5088164774 @default.
- W4361943852 creator A5089632095 @default.
- W4361943852 date "2023-03-31" @default.
- W4361943852 modified "2023-10-14" @default.
- W4361943852 title "Data from An Adenoviral Vaccine Encoding Full-Length Inactivated Human Her2 Exhibits Potent Immunogenicty and Enhanced Therapeutic Efficacy without Oncogenicity" @default.
- W4361943852 doi "https://doi.org/10.1158/1078-0432.c.6518551" @default.
- W4361943852 hasPublicationYear "2023" @default.
- W4361943852 type Work @default.
- W4361943852 citedByCount "0" @default.
- W4361943852 crossrefType "posted-content" @default.
- W4361943852 hasAuthorship W4361943852A5000371531 @default.
- W4361943852 hasAuthorship W4361943852A5008662619 @default.
- W4361943852 hasAuthorship W4361943852A5011368708 @default.
- W4361943852 hasAuthorship W4361943852A5019037704 @default.
- W4361943852 hasAuthorship W4361943852A5020602283 @default.
- W4361943852 hasAuthorship W4361943852A5022822590 @default.
- W4361943852 hasAuthorship W4361943852A5028156079 @default.
- W4361943852 hasAuthorship W4361943852A5044565308 @default.
- W4361943852 hasAuthorship W4361943852A5045134210 @default.
- W4361943852 hasAuthorship W4361943852A5053154937 @default.
- W4361943852 hasAuthorship W4361943852A5054445393 @default.
- W4361943852 hasAuthorship W4361943852A5055582773 @default.
- W4361943852 hasAuthorship W4361943852A5060398911 @default.
- W4361943852 hasAuthorship W4361943852A5075662505 @default.
- W4361943852 hasAuthorship W4361943852A5077597600 @default.
- W4361943852 hasAuthorship W4361943852A5083266436 @default.
- W4361943852 hasAuthorship W4361943852A5088164774 @default.
- W4361943852 hasAuthorship W4361943852A5089632095 @default.
- W4361943852 hasBestOaLocation W43619438522 @default.
- W4361943852 hasConcept C104317684 @default.
- W4361943852 hasConcept C121608353 @default.
- W4361943852 hasConcept C126322002 @default.
- W4361943852 hasConcept C153911025 @default.
- W4361943852 hasConcept C203014093 @default.
- W4361943852 hasConcept C2780868878 @default.
- W4361943852 hasConcept C2781018059 @default.
- W4361943852 hasConcept C29537977 @default.
- W4361943852 hasConcept C32470452 @default.
- W4361943852 hasConcept C40767141 @default.
- W4361943852 hasConcept C502942594 @default.
- W4361943852 hasConcept C55493867 @default.
- W4361943852 hasConcept C71924100 @default.
- W4361943852 hasConcept C86803240 @default.
- W4361943852 hasConcept C8891405 @default.
- W4361943852 hasConceptScore W4361943852C104317684 @default.
- W4361943852 hasConceptScore W4361943852C121608353 @default.
- W4361943852 hasConceptScore W4361943852C126322002 @default.
- W4361943852 hasConceptScore W4361943852C153911025 @default.
- W4361943852 hasConceptScore W4361943852C203014093 @default.
- W4361943852 hasConceptScore W4361943852C2780868878 @default.
- W4361943852 hasConceptScore W4361943852C2781018059 @default.
- W4361943852 hasConceptScore W4361943852C29537977 @default.
- W4361943852 hasConceptScore W4361943852C32470452 @default.
- W4361943852 hasConceptScore W4361943852C40767141 @default.
- W4361943852 hasConceptScore W4361943852C502942594 @default.
- W4361943852 hasConceptScore W4361943852C55493867 @default.
- W4361943852 hasConceptScore W4361943852C71924100 @default.
- W4361943852 hasConceptScore W4361943852C86803240 @default.
- W4361943852 hasConceptScore W4361943852C8891405 @default.
- W4361943852 hasLocation W43619438521 @default.
- W4361943852 hasLocation W43619438522 @default.
- W4361943852 hasOpenAccess W4361943852 @default.
- W4361943852 hasPrimaryLocation W43619438521 @default.
- W4361943852 hasRelatedWork W2350712191 @default.
- W4361943852 hasRelatedWork W2356845216 @default.
- W4361943852 hasRelatedWork W2361163271 @default.
- W4361943852 hasRelatedWork W2364889042 @default.
- W4361943852 hasRelatedWork W2367347076 @default.
- W4361943852 hasRelatedWork W2372688509 @default.
- W4361943852 hasRelatedWork W2380193716 @default.
- W4361943852 hasRelatedWork W2382009198 @default.
- W4361943852 hasRelatedWork W2394525459 @default.
- W4361943852 hasRelatedWork W2410729395 @default.
- W4361943852 isParatext "false" @default.
- W4361943852 isRetracted "false" @default.
- W4361943852 workType "article" @default.