IBT in collaboration with Dr. Jean Lee lab at Brigham and Women Hospital, Harvard University, received a collaborative SBIR grant from NIH, entitled ISTAb: A novel therapy to target staphylococcal toxins at the site of infection.
Staphylococcus aureus (SA) is a Gram-positive human pathogen that causes a wide range of diseases from skin and soft tissue infections (SSTI) to life threatening sepsis and pneumonia. Numerous virulence factors, including cell surface proteins and polysaccharides, as well as secreted toxins are involved in SA pathogenesis. The cytolytic toxins kill key immune cells, allowing the pathogen to evade the immune response, induce tissue damage, and promote bacterial dissemination and metastatic growth in distant organs. There are currently no vaccine or immunotherapeutics against S. aureus.
In this Phase I SBIR, led by Dr. Rajan P. Adhikari, we will target neutralizing anti-toxin antibodies to the site of SA infection by taking advantage of the cell wall targeting (CWT) domain of lysostaphin (lyso) that specifically binds to the SA cell wall. The isolated CWT domain will be fused to specific anti-toxin monoclonal antibodies (mAbs) to generate Infection Site Targeted anti-toxin Antibodies (ISTAbs). A number of engineered candidates will be produced and tested in animal models of S. aureus invasive disease to select a preclinical candidate therapeutic.