1. Abstract 1550: FT576 path to first-of-kind clinical trial: translation of a versatile multi-antigen specific off-the-shelf NK cell for treatment of multiple myeloma
- Author
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Jode P Goodridge, Yu-Waye Chu, Sajid Mahmood, Miguel Meza, Svetlana Gaidarova, Robert Blum, Thomas H. Lee, Jeffrey S. Miller, Brian Groff, Bruce Walcheck, Bahram Valamehr, Frank Cichocki, John Reiser, Greg Bonello, Thomas Daley, Hui-yi Chu, Karl-Johan Malmberg, Ryan Bjordahl, and Armin Rehm
- Subjects
Cancer Research ,Computer science ,Cell ,Translation (biology) ,Computational biology ,medicine.disease ,Clinical trial ,medicine.anatomical_structure ,Oncology ,Antigen specific ,Path (graph theory) ,medicine ,Off the shelf ,Multiple myeloma - Abstract
Chimeric antigen receptor (CAR) directed therapies have been used successfully to treat a variety of hematological malignancies. With the advent of multi-modal engineering, adoptive cell therapy offers the opportunity to tackle increasingly complex disease settings such as multiple myeloma (MM), where targeting of single tumor associated antigen by CAR or monoclonal antibodies (mAb) is confounded by antigen loss and clonal heterogeneity. Further, expanding treatment options beyond primary T and NK cell based therapies has multiple advantages, including the use of induced pluripotent stem cells (iPSC) to derive effector cells using precision genetic engineering that can be uniformly manufactured at scale from a clonally-derived master cell bank (MCB).FT576 is a multiplex-edited, iPSC-derived CAR-NK (CAR-iNK) cell therapy designed for treatment of Multiple Myeloma. FT576 is engineered 1) to express a recombinant IL-15/IL-15 receptor signaling complex (IL-15RF) for enhanced persistence; 2) to express an enhanced high-affinity, non-cleavable CD16 (hnCD16) ; 3) to disrupt expression of CD38, allowing for enhanced ADCC without NK cell fratricide; and 4) to express a BCMA-targeted CAR with NK-cell optimized signaling.CAR-directed specificity of the FT576 cells for BCMA was demonstrated using a short-term cytotoxicity assay (90.8% cytotoxicity against BCMA+ vs 22.1% BCMA- cells, p Citation Format: Jode P. Goodridge, Ryan Bjordahl, Sajid Mahmood, John Reiser, Svetlana Gaidarova, Robert Blum, Frank Cichocki, Hui-yi Chu, Greg Bonello, Tom Lee, Brian Groff, Miguel Meza, Thomas Daley, Yu-waye Chu, Bruce Walcheck, Karl-Johan Malmberg, Jeffrey S. Miller, Armin Rehm, Bahram Valamehr. FT576 path to first-of-kind clinical trial: translation of a versatile multi-antigen specific off-the-shelf NK cell for treatment of multiple myeloma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1550.
- Published
- 2021