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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.
Journal Cancer gene therapy
Vol 18
Issue 1
Date 2011 Jan
URL
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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
ADXS31-164 ADXS31-164 1 1
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