ArticleClinical and vaccine immunology : CVI2008
Optimization of a type III secretion system-based Pseudomonas aeruginosa live vector for antigen delivery.
Article in Clinical and vaccine immunology : CVI, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 25 citations in OpenAlex.
- Bacterial live therapeutics for human diseases.Molecular systems biology · 2024Review
- The role of bacteria and its derived biomaterials in cancer radiotherapy.Acta pharmaceutica Sinica. B · 2023Review
- Recent Advances in Bacteria-Based Cancer Treatment.Cancers · 2022Review
- Review
- Mechanistic research holds promise for bacterial vaccines and phage therapies forDrug design, development and therapy · 2019Review
- Intracellular delivery of biologic therapeutics by bacterial secretion systems.Expert reviews in molecular medicine · 2017Review
- Bacterium-Derived Cell-Penetrating Peptides Deliver Gentamicin To Kill Intracellular Pathogens.Antimicrobial agents and chemotherapy · 2017Article
- Poly-functional and long-lasting anticancer immune response elicited by a safe attenuatedMolecular therapy oncolytics · 2016Article
- A safe bacterial microsyringe for in vivo antigen delivery and immunotherapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Bacterial vectors for active immunotherapy reach clinical and industrial stages.Human vaccines & immunotherapeutics · 2012Review
- High-yield production of secreted active proteins by the Pseudomonas aeruginosa type III secretion system.Applied and environmental microbiology · 2008Article
- Bacterial type III secretion system as a protein delivery tool for a broad range of biomedical applications.Biotechnology advancesReview
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the last few years, the use of type III secretion system-based bacterial vectors for immunotherapy purposes has been assessed in various applications. We showed that a type III secretion-based Pseudomonas aeruginosa vector delivering the ovalbumin (OVA) antigen induced an efficient specific CD8+ T-lymphocyte immune response against OVA-expressing cells. Because of the intrinsic toxicity of the vector, further virulence attenuation was needed. Therefore, we explored the effects of the deletion of quorum-sensing genes and the aroA gene toward toxicity and efficiency of the vector strain. The aroA mutation in our strain (making the strain auxotrophic for aromatic amino acids) conferred a strikingly reduced toxicity, with the bacterial lethal dose being more than 100 times higher than that of the parental strain. The quorum-sensing gene mutation alone was associated with a slightly reduced toxicity. In a prophylactic OVA-expressing melanoma mouse model, an OVA-delivering aroA-deficient mutant was the most efficient at a low dose (10(5)), but dose enhancement was not associated with a greater immune response. The quorum-sensing-deficient strain was the most efficient at a mild dose (10(6)), but this dose was close to the toxic dose. Combination of both mutations conferred the highest efficiency at an elevated dose (10(7)), in agreement with the known negative effects of quorum-sensing molecules upon T-cell activation. In conclusion, we have obtained a promising immunotherapy vector regarding toxicity and efficiency for further developments in both antitumor and anti-infectious strategies.
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