Loyola University Medical Center, Maywood, IL
Courtney Regan , Joseph Clark , Tamson Moore , Kelly Moxley , Gina Scurti , Ann Lau Clark , Boro Dropulic , Heather Embree , Keisuke Shirai , Elizabeth Garrett-Mayer , Mingli Li , Kristen Tobin Vealey , Jonathan M. Eby , Caroline Le Poole , Michael Nishimura
Background: Studies in adoptive T-cell transfer have suggested that persistence of the transduced T-cells is central to the viability of this therapeutic option. The objectives of this phase I clinical trial using TCR TIL 1383I transduced T cells in stage IV melanoma patients include measuring of persistence and monitoring the behavior of tumor-reactive T-cells in vivo. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from three melanoma patients, activated with anti-hCD3 with rhIL2 and rhIL15, transduced with lentivirus encoding the TIL 1383I TCR, and expanded to treatment numbers. The transduced cells were suspended in 5% human albumin and infused over 30 minutes. The infusion was preceded by lymphodepletion with fludarabine and cyclophosphamide and followed with low dose IL-2 for one week. A modified CD34 cassette in the vector enabled monitoring of the transduced T cells in the patient’s PBMC post-infusion. PBMCs were collected from patients on days 1, 3, 5, 7, 14, 25, 35 and monthly up to 3 months and then every 1-3 months as clinically indicated. The presence of transduced T-cells at each time point was measured by staining with anti-CD34 mAb and analyzed using a BD LSRFortessa flow cytometer. Results: Transduced T-cells were detected in the blood of all three patients post infusion. Clinical activity was demonstrated in two patients – one in the form of tumor shrinkage and another with development of progressive vitiligo. Conclusions: Previous studies with TIL suggest better T-cell engraftment, persistence, and therapeutic efficacy with homeostatic proliferation after lymphodepletion. Out results confirm that the infused TIL 1383I TCR transduced T-cells could be detected up to 6 months after infusion and demonstrate activity. Clinical trial information: NCT01586403
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