The adoptive transfer of virus-specific T cells has produced remarkable clinical results in patients with viral disease. However, broader implementation of this therapy has been limited by the (i) prohibitive production costs, (ii) complexity of manufacture, (iii) prolonged time for preparation and product release, and (iv) the requirement for individualized, patient-specific products. Over the past 6 years we have systematically addressed these problems: we simplified and refined our manufacturing technology, removed biohazardous components and employed a new cell expansion platform using a gas permeable culture device which promotes the proliferation and survival of large cell numbers in a GMP-compliant closed system with minimal technician intervention. Finally, we have established the clinical benefit associated with the infusion of partially HLA matched virus-specific T cells that are prospectively generated and banked, making them available for immediate ?off the shelf? use. Thus, with the purpose of moving beyond highly specialized academic centers we established a Baylor College of Medicine-affiliated company called ViraCyte with the goal of commercializing ?off the shelf? virus- specific T cells. Our product - Viralym-A - is a bank of T cell lines with specificity for Adenovirus, which, in immunocompromised individuals, is responsible for a wide range of severe clinical syndromes including pneumonia, hemorrhagic cystitis, nephritis, colitis, hepatitis, and encephalitis, resulting in death in 18-26% of patients. Our therapy is intended for the treatment of drug-resistant infections/disease, a condition that afflicts less than 200,000 persons in the United States and for which there is no standard of care. Thus, in the current application we will test the safety and potential for anti-viral activity of Viralym-A in allogeneic hematopoietic stem cell transplant recipients. Success of this application will lay the foundation for a Phase IIb study to confirm the efficacy of ?off the shelf? Viralym-A cells and facilitate market approval, thereby moving T cell therapy for Adenovirus into the public domain as a standard of care.
The immune system is comprised of specialized cells call ?T cells? that are able to recognize and eliminate opportunistic infections. Therefore, in healthy individual, although viruses can cause mild flu-like symptoms these resolve spontaneously without medical intervention. However, when the integrity of the immune system is compromised [e.g. in babies with genetic immune defects or as a consequence of a medical treatment (eg. after bone marrow transplant)] viral infections may cause severe symptoms in multiple organs, underscoring the need for new and safe approaches to treat infections. Over the past 20 years our scientific team has utilized T cells that were generated in the laboratory to treat drug-resistant infections and we have validated the safety and clinical benefit of this therapy in immune compromised patients. However, despite our success this therapy has not moved beyond academic centers due to the complexity associated with the preparation of T cells. Therefore, for the past 6 years our team has worked diligently to streamline and simplify our cell production process, while maintaining the product integrity. Thus, we are now in a position to transition from an academic center to making this therapy a standard of care. With this objective in mind we established a company called ViraCyte and in the current application we propose testing the safety of our cell product ? Viralym-A ? in bone marrow transplant patients with drug- resistant adenovirus infections. If successful, this work will provide crucial enabling data that will allow us to move towards product approval by testing the clinical efficacy of Viralym-A in a phase IIb clinical trial. We are confident in achieving our goal as the ViraCyte co-founders ? a unique combination of scientists, clinicians and successful entrepreneurs - have a long-standing collaborative relationship and history of success.
