Histamine Receptor 2 Antagonists as Enhancers of Anti-Tumour Immunity
Condition: Cancer
Study type: Interventional
Phase: Phase 4

Summary: 
      The immune response against tumors can be highly effective in preventing tumor development,
      growth and metastasis under certain circumstances. However, tumor associated immune
      suppression can profoundly limit the impact of natural tumor immunity and also reduce the
      effectiveness of tumor immunotherapy strategies.

      A major component of tumor associated immune suppression is mediated by myeloid cells,
      especially the monocytic subset of myeloid derived suppressor cells (MDSC). In recent studies
      that were conducted through a CCSRI Innovation grant, the investigators discovered that oral
      treatment of mice with the commonly used histamine receptor 2 (H2) antagonists ranitidine or
      famotidine inhibits both primary breast tumor development and metastasis, in three distinct
      mouse tumor models and reduces the numbers of monocytic MDSC. These findings have enormous
      potential to aid in effective cancer immunotherapy and may have immediate implications for
      cancer patients.

      The objective of this investigation is to determine whether treatment with the H2 receptor
      antagonist ranitidine alters immune suppression, through modulation of immune cell
      populations.

      The investigators will examine peripheral blood monocyte, neutrophil and NK cell numbers,
      subsets and activation status from healthy volunteers treated for 6 weeks with daily oral
      ranitidine.

      Ranitidine is widely available and used over the counter in Canada. These drugs are widely
      recognized as safe, well tolerated and have very few side effects. It has been suggested that
      among the general population, over 10% of those over the age of 65 take such medications on a
      regular basis for relief against gastrointestinal discomfort. The outcome of pre-clinical
      studies in mice warrant further investigation into transferability to humans.

      If the outcome of the current proposal proves to be viable, then these drugs could provide a
      safe method to reduce tumor associated immunosuppression with broad implications, both for
      current cancer patients and for those at high risk of developing cancer. Further to this, the
      outcome of our proposal may provide a new strategy for improving the effectiveness of T-cell
      mediated immunotherapy.
    


Intervention name(s): Ranitidine
Intervention type(s): Drug
Intervention description(s): Thirty subjects will receive Ranitidine to a maximum of 900 mg/day in 2 daily oral doses for 6 weeks. The dosage target is 8 mg/kg/day, but the range of ranitidine intake will be between 7.5- 9 mg/kg/day. This is due to the formulation of the tablets, sold as 75, 150, and 300mg tablets.
Other intervention name(s): Zantac
Intervention MeSH terms: Ranitidine; Ranitidine bismuth citrate
Intervention model: Single Group Assignment
Intervention model description: Healthy individuals will be asked to take ranitidine for 6 weeks to determine the effect on peripheral blood immune cells.
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Cancer; Immunity; Peripheral Blood Mononuclear Cells; Ranitidine