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A microbial-based cancer vaccine for induction of EGFRvIII-specific CD8+ T cells and anti-tumor immunity
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A microbial-based cancer vaccine for induction of EGFRvIII-specific CD8+ T cells and anti-tumor immunity
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Journal Article
A microbial-based cancer vaccine for induction of EGFRvIII-specific CD8+ T cells and anti-tumor immunity
2019
Overview
Dysregulated signaling via the epidermal growth factor receptor (EGFR)-family is believed to contribute to the progression of a diverse array of cancers. The most common variant of EGFR is EGFRvIII, which results from a consistent and tumor-specific in-frame deletion of exons 2-7 of the EGFR gene. This deletion generates a novel glycine at the junction and leads to constitutive ligand-independent activity. This junction forms a novel shared tumor neo-antigen with demonstrated immunogenicity in both mice and humans. A 21-amino acid peptide spanning the junctional region was selected, and then one or five copies of this 21-AA neo-peptide were incorporated into live-attenuated Listeria monocytogenes-based vaccine vector. These vaccine candidates demonstrated efficient secretion of the recombinant protein and potent induction of EGFRvIII-specific CD8+ T cells, which prevented growth of an EGFRvIII-expressing squamous cell carcinoma. These data demonstrate the potency of a novel cancer-specific vaccine candidate that can elicit EGFRvIII-specific cellular immunity, for the purpose of targeting EGFRvIII positive cancers that are resistant to conventional therapies.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Antigens
/ Cancer
/ Cancer Vaccines - immunology
/ Cancer Vaccines - therapeutic use
/ Carcinoma, Squamous Cell - immunology
/ Carcinoma, Squamous Cell - metabolism
/ Carcinoma, Squamous Cell - therapy
/ CD8-Positive T-Lymphocytes - metabolism
/ Epidermal growth factor receptors
/ Exons
/ Female
/ Glycine
/ Immunity
/ Kinases
/ Listeria
/ Medicine and Health Sciences
/ Mice
/ Motility
/ Peptides
/ Proteins
/ T cells
/ Tumors
/ Vaccines
