University of Pittsburgh researchers have generated genetically modified bacterial strains to deliver therapeutic cytokines to the intestine that may provide lifesaving treatment to individuals suffering from exposure to dangerous levels of radiation.
Description
Patients undergoing radiative therapies for cancer face significant challenges due to radiation damage. Severe total body irradiation can cause extensive damage to intestinal crypt cells and villi, causing breach of the intestinal protective barrier that can lead to sepsis, resulting in death within days. This highlights the urgent need for effective radiation protection and mitigation strategies for patients for which current radiation therapy, despite being the most effective treatment, is too toxic and can destroy intestinal tissue, most notably ovarian cancer patients.
Radiation exposure rapidly depletes crypt cells, intestinal immunocytes (including T-cells that produce anti-inflammatory cytokines like interleukin-22), and goblet cells that produce mucin to protect the intestinal epithelium. High-dose radiation also causes shrinkage of antimicrobial Paneth cells, which produce defensins, lysozymes, and protective cytokine interferon-B. Interleukin-22 has been shown to mitigate intestinal radiation damage and restore Paneth cell functionality if administered 48 hours post-irradiation. Researchers have now developed a novel approach using genetically engineered strains of bacteria, L. reuteri and E. coli, to deliver therapeutic amounts of IL-22 or IFN-B. This innovative microbial therapy offers a promising solution for radiation mitigation and optimizes recovery from total body irradiation.
Applications
• Protection of the intestine during clinical radiotherapy.
• Treatment of irradiation-induced intestinal damage for patients with leukemia, lymphoma, multiple myeloma, neuroblastoma, etc.
Advantages
· Genetically engineered bacteria can be administered by gavage or swallowed
Invention Readiness
• Pre-clinical studies in mice showed efficacy of LR-IL-22.
IP Status
https://patents.google.com/patent/US20220362340A1
