SRL172 (killed Mycobacterium vaccae) may augment the efficacy of trastuzumab in metastatic breast cancer patients

Med Hypotheses. 2005;64(2):248-51. doi: 10.1016/j.mehy.2004.07.016.

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.

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / immunology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology
  • Bacterial Vaccines / therapeutic use*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / therapy*
  • Erb-b2 Receptor Tyrosine Kinases / immunology
  • Female
  • Gene Amplification / drug effects
  • Humans
  • Interleukin-2 / immunology
  • Killer Cells, Natural / immunology
  • Mycobacterium
  • Neoplasm Metastasis / immunology
  • Neoplasm Metastasis / therapy*
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Bacterial Vaccines
  • Interleukin-2
  • Erb-b2 Receptor Tyrosine Kinases
  • Trastuzumab
  • SRL172