Salmonella enterica serovar Typhimurium immunotherapy for B-cell lymphoma induces broad anti-tumour immunity with therapeutic effect.
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.
Laboratory for Vaccine Research, Depto Desarrollo Biotecnológico, Facultad de Medicina, Instituto de Higiene, Universidad de la República, Montevideo, Uruguay; Departamento Básico de Medicina, Facultad de Medicina, Hospital de Clínicas, Universidad de la República, Montevideo, Uruguay.
Sofía
S
Grille
María
M
Moreno
Thais
T
Bascuas
Juan M
JM
Marqués
Natalia
N
Muñoz
Daniela
D
Lens
Jose A
JA
Chabalgoity
D000818:Animals; D016923:Cell Death / Q000276:immunology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D005260:Female; D056724:Immunity, Humoral; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D007962:Leukocytes / Q000276:immunology / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy; D051379:Mice; D012486:Salmonella typhimurium / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology
D000939:Epitopes; D007371:Interferon-gamma
bacteria; tumour immunology; vaccination