Developing a Manufacturing Process for Therapeutic Exosomes
Abstract
The product to be developed addresses the Fiscal Year 2015 Peer Reviewed Medical Research Program Topic Area of Cardiovascular Health and is also possibly applicable broadly across other disease areas in which scar formation and inflammation are features. The product is a nanometer-sized particle, the type of which can be found in nearly every fluid of the body, known to act as a long distance messenger in the body. These particles, called exosomes, carry messages encoded by genetic material that they inherit from the cell that gave rise to them. Particular cell types give rise to exosomes with particular messages, and cells can be made to do so while in culture in a laboratory. We have a process for collecting exosomes from cultured cells and packaging them as a medicine (yet to be approved by the Food and Drug Administration). We also have a specialized cell from which the exosomes are derived, one which is itself currently under evaluation in several clinical trials ongoing in the United States. These cells are grown from donated human hearts, originate from the heart, and are apt at treating heart disease and repairing heart damage after injury. Their exosomes are similarly endowed. These biologics, more specifically cell therapies as they are known, are a new and evolving therapeutic class. The hope for these cell therapies is that patients will experience an immediate repair of heart damage and will ultimately experience an improved quality of life and longer life due to the fact that these therapies have a durable effect. However, none of these novel therapies are yet approved by the Food and Drug Administration for the treatment of heart disease, and many of them are cumbersome to handle. Their inherent awkwardness, related to the fact that living cells require deep freezing and specialized handling, will limit their adoption and widespread use even after approval. Exosomes are an opportunity to circumvent that. Exosomes can be freeze dried, could potentially be stored under any conditions, and yet retain the same therapeutic properties as their parent cells when collected with care. However, this ideal biologic is in many ways still an ideal. The current project proposes to make it a reality. The current process we utilize for collecting exosomes cannot practically or economically be scaled up to ever meet commercial demand, particularly for an indication as large as heart disease. That being said, there are technologies in existence, bioreactors currently used to manufacture viruses and antibodies, that could be adopted for purposes of large-scale exosome manufacturing. We intend to do just that. The first half of the project will be spent transitioning the current process to a large-scale bioreactor platform. The second half of the project will be spent working toward the ideal freeze-dried product and ensuring that proper care has been taken and the product remains unaltered from the original. This so-called process development work we will undertake is a lengthy and expensive exercise, particularly when it comes to biologics, which are not defined by a simple chemical structure but rather by their bioactive features. These features often require testing using other cells as model systems or even animal models, and the readouts are inherently graded and shaded. Thus, process development is iterative and repetitive to ensure that the product s integrity remains intact. While this exosome process development work is ongoing, clinical development by the applicant will occur in parallel. The current collection process is appropriate for manufacturing exosomes for use in a clinical trial, and approval from the Food and Drug Administration to do so will soon be sought. These steps will lead in the near future to the approval of exosomes for the treatment of heart disease. If the proposed process development work is funded, large-scale exosome production will be possible when that time comes
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610712
Entities
People
- Rachel J Smith
Organizations
- United States Army