PANTIPA—Preclinical development of patient-derived monoclonal antibodies targeting Pseudomonas aeruginosa
Pseudomonas aeruginosa is a multidrug-resistant bacterium that can cause life-threatening infections, such as sepsis and pneumonia. One of the key weapons used by this bacterium is the type III secretion system (T3SS), which contains the protein PcrV. Researchers at the DZIF discovered that patients with chronic infections develop highly effective antibodies against PcrV. Based on this finding, they produced monoclonal antibodies (mAbs) that block the T3SS and neutralize P. aeruginosa's virulence. The project's goal is to identify the most promising mAb for human use and produce it under strictly controlled conditions. Safety and efficacy are being tested in preclinical studies to pave the way for initial clinical trials. The goal is to develop a novel drug to treat acute infections and prevent them in high-risk patients.
New targets against a dangerous pathogen
Antimicrobial resistance represents one of the major challenges in modern medicine. In this context, Pseudomonas aeruginosa (PA) stands out as a notorious multidrug-resistant pathogen that frequently evades treatment with standard antibiotics. It can lead to life-threatening infections, such as pneumonia, wound infections, and sepsis, especially in seriously ill or immunocompromised patients. The World Health Organization (WHO) considers PA to be one of the pathogens for which new treatment options must be developed urgently.
PA has a particularly dangerous mechanism: the type III secretion system (T3SS). It allows PA to inject toxic proteins directly into human cells, worsening the course of the disease. A central component of this system is the PcrV protein, which acts as a "key" for the bacterium's attack. Blocking PcrV renders the T3SS harmless and reduces the bacterium's danger.
Antibodies as a promising therapeutic approach
Researchers at the DZIF discovered that people infected with PA for a long time produce highly effective PcrV-specific antibodies. These antibodies are natural defenses produced by our immune system that can specifically recognize and neutralize pathogens or their components. Based on this finding, monoclonal antibodies (mAbs) that directly target PcrV were produced in the laboratory. Initial studies show that these antibodies can completely block the effect of the T3SS and act similarly to antibiotics in animal models.
Project objectives
The current project aims to select the best candidate antibody for use in humans.
- Preclinical Phase: Extensive laboratory and animal testing will be conducted to determine which antibody offers the best combination of efficacy, stability, and tolerability.
- Production for clinical trials: The selected antibody will then be produced in cell cultures under strictly controlled conditions (Good Manufacturing Practice, or GMP). This "clinical material" will be tested for safety and efficacy.
The goal of this project is to develop a human-derived anti-PcrV antibody for clinical use for the first time. The long-term vision is a new, targeted drug to treat acute Pseudomonas infections, such as sepsis or pneumonia. It will also be used to passively immunize high-risk patients in hospitals.
