Science Advance: ACTSI Supported T1 Research at Emory University-Innovative Cellular Therapy to Treat Crohn's Disease

Crohn's disease (CD) and ulcerative colitis (UC) collectively known as inflammatory bowel disease (IBD) is a chronic, life-long disorder with devastating consequences including substantial morbidity and increased mortality. Newly emerging anti-TNF biologic treatments are effective; however, enthusiasm over their use, particularly in children, is tempered by the concerns of serious side effects including life-threatening infections, severe allergic reactions and malignancies. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has a long history of funding scientific and therapeutic studies in IBD, and is currently funding Dr. Subra Kugathasan at Emory University (Gene Discoveries in Subjects with Crohn's Disease of African Descent) to further extend novel genomic discoveries in IBD into new diagnostic, risk stratification, and therapeutics. To further address the unmet clinical and therapeutic needs of this population, Dr. Kugathasan and other Emory collaborators have joined the Emory Personalized Immunotherapy Center (EPIC), a unique cellular therapy center, to develop an innovative cellular therapy for IBD using mesenchymal stromal cells (MSCs) which have emerged as a novel approach for immune related disorders like IBD, as MSCs have been shown to have a broad spectrum of suppressive actions on both the innate and adaptive immune systems.

EPIC offers patients access to cutting edge, innovative personalized cellular pharmaceuticals for treatment of human catastrophic illnesses arising from immune dysfunction by translating innovations in personalized cell therapy to first-in-human clinical trials, including pediatric clinical applications with Children's Healthcare of Atlanta (Children's). Two Emory teams comprise EPIC - the EPIC Cell Processing core team and the Children's IBD translational team. The EPIC Cell Processing core team led by Dr. Jacques Galipeau, uses a 1,000 ft2 clinical-grade, fully equipped, high sterility isolation facility staffed by a team of highly qualified personnel dedicated to manufacturing cellular therapies under FDA compliant good manufacturing practices (cGMP) for the successful implementation and prosecution of personalized cellular medicine clinical trials. The Children's IBD translational team consists of 12 individuals led by Dr. Kugathasan which will test this novel therapeutic in pediatric IBD.

The single most important extramural regulatory requirement for investigator-sponsored clinical trials is obtaining an IND from FDA. Navigating the path towards regulatory approval of a trial testing a novel autologous cell therapy product is complex and requires satisfactory data regarding: clinical trial design; product manufacturing; and pre-clinical (animal and in vitro) data in support of trial and manufacturing. With pilot funding from the ACTSI Pilot Grants program, a preclinical feasibility study testing MSCs was completed using 10 adolescents with IBD and a fetal bovine serum (FBS)-free GMP-compliant method for tissue culture expansion of low passage MSCs using allogeneic human platelet-lysate (phPL) was optimized to maximize the immunosuppressive capabilities of the cells and to minimize their potential immune rejection, thus delivering a highly efficacious product while eliminating toxicities. With ACTSI Pilot Grants and Pediatrics support, IND and Emory IRB approval were obtained and intramural clinical trials oversight navigated, creating the pathway for recruitment of initial first-in-man trial subject which occurred in July 2012. This experience demonstrates how CTSA resources can be used to assist University-based, NIH sponsor-investigators to apply for and obtain novel INDs from FDA CBER in the domain of cellular therapies and to subsequently navigate the regulatory requirements to promptly initiate innovative first-in-human studies.

IND and the companion Phase I clinical trial represents a new partnership between Emory and Children's supported by the NIH to advance innovative healthcare for Georgia and beyond, which is quite literally a new level of first-in-human care and discovery. The experience of utilizing CTSA, NIH, and institutional resources to expedite therapeutic development is likely applicable to other research-focused academic institutions nationwide. Continuing and future support from the ACTSI will be instrumental in delivering the promise of this new therapy to the IBD population.

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