Salmonella enterica serovar Typhimurium immunotherapy for B-cell lymphoma induces broad anti-tumour immunity with therapeutic effect

Immunology. 2014 Nov;143(3):428-37. doi: 10.1111/imm.12320.

Abstract

Despite the efficacy of current immune-chemotherapy for treatment of B-cell non-Hodgkin lymphoma, a substantial proportion of patients relapse, highlighting the need for new therapeutic modalities. The use of live microorganisms to develop anti-tumoural therapies has evolved since Coley's toxin and is now receiving renewed attention. Salmonella Typhimurium has been shown to be highly effective as an anti-tumour agent in many solid cancer models, but it has not been used in haemato-oncology. Here, we report that intra-tumoural administration of LVR01 (attenuated S. Typhimurium strain with safety profile) elicits local and systemic anti-tumour immunity, resulting in extended survival in a lymphoma model. LVR01 induces intra-tumoural recruitment of neutrophils and activated CD8(+) T cells, as well as increasing the natural killer cell activation status. Furthermore, a systemic specific anti-tumour response with a clear T helper type 1 profile was observed. This approach is an alternative therapeutic strategy for lymphoma patients that could be easily moved into clinical trials.

Keywords: bacteria; tumour immunology; vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / immunology
  • Cell Line, Tumor
  • Disease Models, Animal
  • Epitopes / immunology
  • Female
  • Immunity, Humoral
  • Immunotherapy / methods*
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Leukocytes / immunology
  • Leukocytes / pathology
  • Lymphoma, B-Cell / genetics
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / mortality
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy
  • Mice
  • Salmonella typhimurium / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / microbiology

Substances

  • Epitopes
  • Interferon-gamma