Central Production and Multi-Site Distribution of Expanded Donor Derived Natural Killer (NK) Cell Immunotherapy in Time Sensitive Clinical Situations — ASN Events
  1. Schedule
  2. Poster Session Two
  3. Central Production and Multi-Site Distribution of Expanded Donor Derived Natural Killer (NK) Cell Immunotherapy in Time Sensitive Clinical Situations

Central Production and Multi-Site Distribution of Expanded Donor Derived Natural Killer (NK) Cell Immunotherapy in Time Sensitive Clinical Situations (#238)

Monica S. Thakar 1 , Hemalatha Rangarajan 2 , Prithy C. Martis 3 , Lawrence S. Gazda 3 , Margaret Lamb 2 , Karely M. van Thiel Berghuijs 4 , Elizabeth Gourdine 5 , Michelle Watts 2 , Michael A. Pulsipher 4 , Dean Lee 2
  1. Clinical Research Division, Fred Hutchinson Cancer Center and University of Washington, Seattle, WA, United States
  2. Hem/Onc/BMT, Nationwide Children’s Hospital, Columbus, OH, United States
  3. Biologics Manufacturing Resource, Abigail Wexner Research Institute of Nationwide Children’s Hospital, Columbus, OH, United States
  4. Division of Pediatric Hematology and Oncology, Intermountain Primary Children’s Hospital, Huntsman Cancer Institute, Spencer Fox Eccles School of Medicine at the University of Utah, Salt Lake City, UT, United States
  5. Pediatric Transplantation and Cellular Therapy Consortium (PTCTC), Children’s Hospital of Los Angeles, Los Angeles, CA, United States

Background: PTCTC is conducting a Phase II study at 13 sites testing the safety/efficacy of prophylactic infusions of donor-derived NK cells after haploidentical hematopoietic cell transplantation (HCT) in children with high-risk acute myelogenous leukemia to prevent relapse, with enrollment of 30 donor-recipient pairs. Central manufacturing requires close communication with sites, avoids duplication of resources, and improves manufacturing consistency in a time-sensitve manner.

Methods: One pint (≤450 mL) of donor whole blood was shipped overnight at ambient temperature to the manufacturing site. NK cells were expanded in Xuri bioreactors for 2 weeks with K562 feeder cells expressing mbIL-21 and 4-1BBL. After release testing, 3 patient-specific NK aliquots (1e8/kg cryopreserved) were delivered to sites via LN2 dry shipper and infused at days -1, +7, and +42 after HCT. If manufacturing resulted in poor yield, patients could remain on study if they received at least the day +7 NK infusion.

Results: To date, 33 manufacturing runs produced 26 products from 26 donors. Final products had a high NK content (median 96%, range 80.36-99.07%) and a negligible T-cell content (median 0.02%, range 0-0.17%). Products had a median 2,956X-fold expansion (range 284-21,680X) and median 11 (range 2-61) doses manufactured per patient. In three cases, receipt of donor blood was delayed 2-4 days, requiring recollection of donor blood in one case. Seven manufacturing runs required utilization of day 7 expansion (n=6) or day 0 (n=1) freeze back material with excellent results. Average final viability of 29 expansions was 93.64%. Clinically, there have been no infusional toxicities or cytokine release syndrome. One subject experienced post-HCT relapse, and under a separate eIND, received 5 extra NK cell doses previously stored as backup.

Conclusions: Allogeneic NK cells can be centrally manufactured in a safe, time-sensitive, and prospective manner from a single pint of peripheral blood and distributed nationally.