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- W4361949551 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.
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- W4361949551 date "2023-03-31" @default.
- W4361949551 modified "2023-09-26" @default.
- W4361949551 title "Data from An Adenoviral Vaccine Encoding Full-Length Inactivated Human Her2 Exhibits Potent Immunogenicty and Enhanced Therapeutic Efficacy without Oncogenicity" @default.
- W4361949551 doi "https://doi.org/10.1158/1078-0432.c.6518551.v1" @default.
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