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Ref Type | Journal Article | ||||||||||||
PMID | (20725099) | ||||||||||||
Authors | Shahabi V, Seavey MM, Maciag PC, Rivera S, Wallecha A | ||||||||||||
Title | Development of a live and highly attenuated Listeria monocytogenes-based vaccine for the treatment of Her2/neu-overexpressing cancers in human. | ||||||||||||
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Abstract Text | A chimeric human Her2/neu gene (ChHer2) harboring most of the known major histocompatibility complex class I epitopes of the HER2/neu oncogene was expressed as a fusion protein to a non-hemolytic fragment of listeriolysin O (LLO), by the highly attenuated Listeria vector LmddA, which lacks antibiotic selection markers and the ability to spread from cell-to-cell. This construct (ADXS31-164) was tested for immunogenicity and anti-tumor effects in mice. Despite being highly attenuated, ADXS31-164 proved to be efficacious in breaking immune tolerance toward the HER2/neu self-antigen. ADXS31-164 elicited strong T-cell immune responses in experimental animals. In tumors, ADXS31-164 caused a reduction in regulatory T cells (Treg) accompanied by an increase in the CD8(+)/Treg ratio. Comparison of this vaccine with the conventional antibiotic resistant Listeria vector (Lm-LLO-ChHer2) shows that ADXS31-164 is more efficacious in delaying tumor growth in Her2/neu transgenic animals. Because of its well-defined attenuation mechanism and independence from antibiotic selection markers, ADXS31-164 is potentially more suitable for human use. These results support the future clinical development of this vaccine for the treatment of HER2/neu-overexpressing malignancies, such as breast, colorectal and pancreatic cancers. |
Molecular Profile | Treatment Approach |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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ADXS31-164 | ADXS31-164 | 0 | 2 |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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ADXS31-164 | ADXS 31164|ADXS-HER2|OST-HER2|OST31 164|OST31164|OST31-164 | ADXS31-164 comprises a live-attenuated Listeria monocytogenes strain engineered to express a fusion protein containing Erbb2 (Her2) epitopes and a fragment of the listeriolysin O (LLO) protein, which may induce an anti-tumor immune response (PMID: 20725099). |
Gene | Variant | Impact | Protein Effect | Variant Description | Associated with drug Resistance |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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