-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1455 Large Scale Ex Vivo Expansion of Γδ T Cells Using Artificial Antigen Presenting Cells for the Treatment of Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 711. Cell Collection and Processing: Poster I
Hematology Disease Topics & Pathways:
AML, Biological, Diseases, Therapies, Technology and Procedures, cell expansion, immunotherapy, Myeloid Malignancies, Clinically relevant
Saturday, December 5, 2020, 7:00 AM-3:30 PM

Justin C. Boucher, PhD1, Bin Yu2*, Gongbo Li, PhD, MBBS3*, Bishwas Shrestha, PhD3, Jeffrey E. Lancet, MD4, David A. Sallman, MD5, Ana Marie Landin6*, Adam William Mailloux, PhD6*, Claudio Anasetti, MD7, Linda L. Kelley, PhD8, Marco L. Davila, MD, PhD3 and Nelli Bejanyan, MD9

1Clinical Science Division, Moffitt Cancer Center, Tampa, FL
2Clinical Science, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
3Clinical Science Division, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
4Malignant Hematology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
5Malignant Hematology Department, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL
6Cell Therapy Facility, H. Lee Moffitt Cancer Center, Tampa, FL
7Department of Blood and Marrow Transplant and Cellular Immunotherapy, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
8Cell Therapy Facility, Moffitt Cancer Center, Tampa, FL
9Department of Blood and Marrow Transplantation and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL

Patients with relapsed or refractory acute myeloid leukemia (AML) are at increased risk of mortality. Higher γδ T cell count in a bone marrow or peripheral blood of patients with leukemia is associated with better survival. However, γδ T cells are rare in the blood and functionally impaired or exhausted in patients with malignancies. Promising results are reported on the treatment of various malignancies with in vivo expansion of autologous γδ T cells using zoledronic acid (zol) and IL-2. Here we demonstrated that zol and IL-2, in combination with a novel genetically engineered K562 CD3/CD137L/CD28/IL15RA quadruplet artificial antigen presenting cell (aAPC), efficiently expand allogeneic donor-derived γδ T cells using a GMP-compliant protocol sufficient to achieve cell doses for future clinical use. We achieved a 633-fold expansion of γδ T cells after day 10 of co-culture with aAPC, the majority of which exhibited central (47%) and effector (43%) memory phenotypes. Additionally, >90% of the expanded γδ T cells expressed NKG2D, while they have low cell surface expression of PD1 and LAG2 inhibitory checkpoint receptors. In vitro real-time cytotoxicity analysis showed that expanded, previously cryopreserved, γδ T cells were effective in killing target cells. Our results demonstrate that large scale ex vivo expansion of donor-derived γδ T cells can be achieved with the use of CD3/CD137L/CD28/IL15RA quadruplet aAPC and zol/IL-2 for clinical application as promising antineoplastic immunotherapy.

Disclosures: Lancet: Abbvie: Consultancy; Agios Pharmaceuticals: Consultancy, Honoraria; Astellas Pharma: Consultancy; Celgene: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; ElevateBio Management: Consultancy; Jazz Pharmaceuticals: Consultancy; Pfizer: Consultancy. Sallman: Celgene, Jazz Pharma: Research Funding; Agios, Bristol Myers Squibb, Celyad Oncology, Incyte, Intellia Therapeutics, Kite Pharma, Novartis, Syndax: Consultancy. Bejanyan: Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees.

<< Previous Abstract | Next Abstract
*signifies non-member of ASH