title: SRL172 (killed Mycobacterium vaccae) may augment the efficacy of trastuzumab in metastatic breast cancer patients.
abstract: SRL172, non-specific immunological adjuvant downregulates interleukin-4, upregulates interleukin-2 production, switching towards a T-helper-1 response, induces an increase in natural killer cells and activates antigen presenting cells. The human epidermal growth factor receptor 2 gene amplification is frequently observed in a number of primary tumors, suggesting that the overexpression of this growth factor receptor may contribute to transformation and tumorigenesis. Gene amplification occurs in approximately 15-20% of human breast cancers Amplification is associated with aggressive tumor behavior and shortened survival. Trastuzumab, humanized anti-HER-2 antibody targets the HER-2 protein with high affinity. Trastuzumab when used alone or in combination with cytotoxic chemotherapy can induce reasonably durable remissions in a significant percentage of women with metastatic breast cancer whose tumors demonstrate Her-2/neu gene amplification. One of the proposed mechanisms of trastuzumab antitumor action is through antibody dependent cellular cytotoxocity. Pivotal study showed that Trastuzumab+IL-2 resulted in NK cell expansion with enhanced in vitro targeted killing of HER-2-expressing cells. SRL172 by increasing IL-2 production and number of natural killer cells may augment the efficacy of trastuzumab in metastatic breast cancer patients. SRL 172 increases IL-2 production and the number of NK cells in vivo. Based on these data, a clinical trial can be performed to test whether SRL 172 added to trastuzumab is safe and more efficacious.
authors.affiliation: Department of Medical Oncology, Faculty of Medicine, Institute of Oncology, Hacettepe University, Sihhiye, 06100 Ankara, Turkey. drkadri@usa.net
authors.forename: Kadri
authors.initials: K
authors.lastname: Altundag
authors.forename: Ali-Seyed
authors.initials: AS
authors.lastname: Mohamed
authors.forename: Ozden
authors.initials: O
authors.lastname: Altundag
authors.forename: Yavuz Selim
authors.initials: YS
authors.lastname: Silay
authors.forename: Esra
authors.initials: E
authors.lastname: Gunduz
authors.forename: Kadir
authors.initials: K
authors.lastname: Demircan
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000276:immunology / Q000627:therapeutic use*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D005784:Gene Amplification / Q000187:drug effects; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D009161:Mycobacterium; D009362:Neoplasm Metastasis / Q000276:immunology / Q000628:therapy*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology; D000068878:Trastuzumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001428:Bacterial Vaccines; D007376:Interleukin-2; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C451081:SRL172