Adoptive Transfer of Engineered Macrophages

The Need

Cell therapies have received recent approvals for immunomodulatory indications. Immuno-activating chimeric antigen receptor (CAR)–T cells have been developed for cancers, whereas immunosuppressive mesenchymal stromal cells (MSCs) have been approved for inflammatory bowel disease and critical limb ischemia. Monocytes/macrophages are another immune cell type that is receiving significant interest as a clinical candidate. Their presence in most tissues as resident cells and in the circulation as patrollers, as well as their involvement in the clearance of injury or infection and subsequent tissue repair make them an intriguing clinical candidate as a cellular therapeutic.

The Technology

Researchers at The Ohio State University led by Dr. Yizhou Dong have been engineering bone marrow derived macrophages for the purpose of developing novel therapeutic interventions. Their most recent published work demonstrates the use of engineered macrophages as an effective treatment for ARB-dependent sepsis. To do this, lipid-like nanoparticles are pre-loaded with mRNA transcripts that encode antimicrobial enzymes. The nanoparticles are delivered to a patient’s macrophages, which deliver the mRNAs to be translated by the cell. After the treated cells are delivered and antimicrobial enzymes are produced, these macrophages encompass and successfully phagocytose ARB. In effect, this process facilitates a successful immune response and compensates for the absence of effective small molecule treatments. Recent in vivo experiments provide support for this technology, with results that indicate this cell therapy markedly decreases the population of bacteria surviving in macrophages and substantially increases survival of sepsis. Therefore, this technology could be developed as a new approach to treating sepsis caused by drug-resistant bacterial infection.

Commercial Applications

  • Platform technology to develop a number of various engineered macrophages
  • New generation of antimicrobial therapy
  • Effective treatment against antimicrobial-resistant bacteria

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