Exosome RNA Exosome RNA Research & Industry News
Codiak BioSciences, Inc., a company at the forefront of advancing engineered exosomes as a new class of biologic medicines, today announced new preclinical data on programs using its proprietary engEx Platform. Highlights include new preclinical data demonstrating the powerful adaptive immune response driven by its exoVACC™ vaccine platform compared to standard vaccine approaches and the first data on its ability to utilize engEx to direct tropism for multiple cell types in vitro and in vivo. These data, which were presented at the 23rd Annual Meeting of the American Society of Gene & Cell Therapy (ASCGT), demonstrate the broad potential of engineered exosomes to serve as a foundation for new classes of molecular medicines to address complex, immune-mediated diseases.
Exosomes are an important intercellular communication system, facilitating the transfer of molecular payloads between cells. They are mediated by a complex network of proteins and glycoproteins on the exosome surface that play a role in cellular tropism, uptake and immune cell signaling. Utilizing its engEx Platform, Codiak can engineer exosomes with distinct properties, load them with various types of therapeutic molecules and alter tropism so they reach specific cell targets. Codiak is developing exosome product candidates to target multiple pathways throughout the body to treat various forms of cancer and, through its exoVACC modular vaccine platform, to enhance the immune response against a broad array of antigens.
“The results that we are generating across our engEx Platform continue to confirm the potential of our engEx engineered exosomes to be an entirely new modality capable of addressing diseases with unmet needs,” said Douglas E. Williams, President and Chief Executive Officer of Codiak BioSciences. “Excitingly, here we debut data generated from our exoVACC platform demonstrating that we can stimulate a holistic and superior immune response via multiple routes of administration compared to conventional vaccine formulations. Our exoVACC data suggest broad potential applications in cancers and infectious diseases.”
exoVACC Induces Potent Systemic and Tissue Resident Immune Responses
exoVACC utilizes the unique properties of Codiak’s engineered exosomes to deliver antigens and adjuvants simultaneously and selectively to antigen presenting cells (APCs), driving an integrated innate, cellular and antibody mediated immune response directed against an antigen. The modularity of the platform allows for the incorporation of multiple complex antigens, adjuvants, targeting ligands and immune co-stimulatory molecules within a single exosome to tailor an appropriate immune response.
To assess immune responses through different routes of administration, exosomes were engineered to express a model antigen ovalbumin (OVA) in the lumen using a proprietary scaffold protein, BASP-1, and were loaded with a STING agonist adjuvant. A single dose of exoVACC induced approximately 9 to 20-fold greater numbers of splenic antigen specific CD8+ T effector memory cells when administered subcutaneously (SC), intranasally (IN) or intravenously (IV) compared to commonly used soluble OVA antigens and an AddaVax ® adjuvant administered SC. To assess the impact of the CD8+ T cell response, exoVACC was evaluated in a lymphoma tumor model. exoVACC attenuated or completely inhibited tumor growth of EG7 OVA and prolonged survival compared to control.
In addition, IN administration of exoVACC resulted in the generation of tissue resident CD8+ T cells in the lung that were absent with a commonly used adjuvant, such as Heltinol®, co-administered with soluble OVA or exosome-associated OVA. These memory tissue resident T cells provide the first line of defense against respiratory viruses, such as SARS-CoV-2.
Engineering Exosomes with Altered Cellular Tropism Results in Targeted Payload Delivery
Results from multiple studies in vitro and in vivo demonstrated the ability of the engEx Platform to redirect exosome tropism and drive uptake in various unique cell types. Several types of targeting domains were displayed on the surface of exosomes. In vivo, increased tropism to both dendritic cells and T cells was achieved. Specifically, decorating exosomes with a targeting domain resulted in a greater number of target cells that had taken up the exosomes, four-fold for anti-Clec9A exosomes in dendritic cells and up to 4.7-fold for anti-CD3 exosomes in T cells, as well as a greater number of exosomes taken up by each cell, six times higher for anti-Clec9A and up to 13 times higher for anti-CD3, when compared to an untargeted exosome control.
Demonstrating that altered tropism leads to increased pharmacological payload delivery, anti-Clec9A exosomes loaded with a STING agonist induced pro-inflammatory cytokines in primary mouse dendritic cells at levels up to 15-fold greater than an untargeted control. In addition, preliminary in vivo data suggest that these anti-Clec9A exosomes reduce the required STING agonist dose 10-fold to control tumor growth and induce immune responses against tumor-associated antigens when compared to untargeted controls.
Source – BusinessWire
