Path to Commercialization of the first “off the shelf” T cell product

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ABSTRACT 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-B - is a bank of T cell lines with specificity for BK virus, which, in immunocompromised individuals including children, is responsible for severe clinical syndromes like hemorragic cystitis and nephropathy that can lead to significant morbidity and prolonged hospital stay. 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-B in allogeneic hematopoietic stem cell transplant recipients. In addition, we will further de-risk the transfer of this technology to a private sector contract manufacturing organization (CMO) by transitioning our cell production from an open to an entirely closed system and validating our scale-up manufacture protocol. Success of this application will lay the foundation for a Phase IIb study to confirm the efficacy of “off the shelf” Viralym-B cells and facilitate market approval, thereby moving T cell therapy for BK virus into the public domain as a standard of care.