Anti-tumor effects of the bacterium Caulobacter crescentus in murine tumor models.
Caulobacter crescentus is a gram negative, non-pathogenic bacterium, common in aquatic and soil environments. One feature of note is a protein surface layer (S-layer) composed of a single protein, organized as a self-assembled crystalline array that coats the bacterium. In the course of efforts to express cancer-associated peptides as genetic insertions into the S-layer, we noted a tumor suppressive effect of the unmodified bacterium. C. crescentus was examined for anti-tumor activity against three transplantable tumor mouse models: Lewis lung carcinoma cells transfected with the MUC1 gene in C57BL/6, murine mammary carcinoma (EMT-6) in BALB/c (both in prophylactic and therapeutic mode) and murine leukemia cells (L1210) in DBA2. Mice were immunized three times i.p. with C. crescentus (2 x 10(7) cells/mouse). In prophylactic mode, the mice were challenged with tumor cells two weeks after the last immunization. Immunization with live C. crescentus resulted in anti-tumor activity in all three transplantable tumor models, as measured by prolonged survival, reduced tumor mass or reduced number of lung nodules, compared to saline control groups. In the Lewis lung and the EMT-6 mammary carcinoma murine models the number of lung nodules as well as the tumor weight was lower in mice treated with C. crescentus, compared to the control group; for EMT-6, this was observed in prophylactic and therapeutic modes. In the murine leukemia and Lewis lung carcinoma models prolonged survival was observed in the groups of mice immunized with Caulobacters. In most cases the live C. crescentus cells were markedly more efficacious than heat killed or formalin fixed cells, despite the fact that they do not grow or persist in mice. The results suggest that C. crescentus may be a safe, bacterial immunomodulator for the treatment of tumors.
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
P K
PK
Bhatnagar
A
A
Awasthi
J F
JF
Nomellini
J
J
Smit
M R
MR
Suresh
D000818:Animals; D000951:Antigens, Neoplasm / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D016935:Caulobacter crescentus / Q000502:physiology*; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy; D006801:Humans; D007114:Immunization; D007939:Leukemia L1210 / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018396:Mucin-1; D009077:Mucins / Q000627:therapeutic use; D014407:Tumor Cells, Cultured / Q000637:transplantation
D000951:Antigens, Neoplasm; C060192:MUC1 protein, human; D018396:Mucin-1; D009077:Mucins