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|Ref Type||Journal Article|
|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.|
|Journal||Cancer gene therapy|
|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|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|ADXS31-164||ADXS31-164 consists of a live attenuated Listeria monocytogenes encoding Erbb2 (Her2) and listeriolysin O (LLO) fusion protein which may have immunostimulatory and antitumor activities (PMID: 20725099).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|ERBB2 over exp||Her2-receptor positive breast cancer||sensitive||ADXS31-164||Preclinical||Actionable||In a preclinical study, ADXS31-164 prevented development of spontaneous mammary tumors in Erbb2 (Her2)-over expressing transgenic animal models (PMID: 20725099).||20725099|