GMP-Compliant Universal Antigen Presenting Cells (uAPC) Promote the Metabolic Fitness and Antitumor Activity of Armored Cord Blood CAR-NK Cells

• DOI: 10.3389/fimmu.2021.626098
• Publication Date: 2021-02-26T04:29:41Z
• Authors: Enli Liu; Sonny O. T. Ang; Lucila Kerbauy; Rafet Basar; Indreshpal Kaur; Mecit Kaplan; Li Li; Yijiu Tong; May Daher; Emily L. Ensley; Nadima Uprety; Ana Karen Nunez C...; Ryan Z. Yang; Ye Li; Hila Shaim; Francia Reyes Silva; Paul Lin; Vakul Mohanty; Sunil Acharya; Mayra Shanley; Luis Muniz-Feliciano; Pinaki P. Banerjee; Ken Chen; Richard E. Champlin; Elizabeth J. Shpall; Katayoun Rezvani
• Keywords: Cancer Immunotherapy; Lymphokine-activated killer cell; Adoptive Cell Transfer; NK-92; Cell therapy

Natural killer (NK) cells are innate lymphocytes recognized for their important role against tumor cells. NK expressing chimeric antigen receptors (CARs) have enhanced effector function various type of cancer and attractive contenders the next generation immunotherapies. However, a number factors hindered application cellular therapy, including poor in vitro growth kinetics relatively low starting percentages within mononuclear cell fraction peripheral blood or cord (CB). To overcome these limitations, we genetically-engineered human leukocyte (HLA)-A − HLA-B K562 to enforce expression CD48, 4-1BBL, membrane-bound IL-21 (mbIL21), creating universal presenting (uAPC) capable stimulating cognate on We shown that uAPC can drive expansion both non-transduced (NT) CAR-transduced CB derived by >900-fold 2 weeks co-culture with excellent purity (>99.9%) without indications senescence/exhaustion. confirmed uAPC-expanded research- clinical-grade NT higher metabolic fitness display targets compared corresponding fractions cultured uAPCs. This novel approach allowed highly pure GMP-grade CAR at optimal numbers be used adoptive cell-based immunotherapy.