Measuring T‐cell avidity and enrichment using acoustic force‐based technology

Abstract

A key metric in the development of effective immunotherapies is the overall interaction strength between an immune cell and a target cell. The parameter describing this cell‐cell interaction strength is termed avidity; and refers to the measurement of the cumulative non‐covalent bond affinities between an immune cell and a target cell. Studies in adoptive cell transfer and antibody‐based therapeutics have shown that cell binding avidity of an immune cell to its target is a better predictor of its function than single molecule affinity measurements and that this parameter is integral to the development of long‐lasting and potent immune responses. The z‐Movi™ technology uses acoustic forces to effectively discriminate immune cells based on their avidity to target cells (e.g. tumor cells) in a high‐throughput manner. We have applied our technology to characterize bispecific antibody interactions, as well as TCR‐T and CAR‐T adoptive cell therapies. Here, we present the workflow of an example study in which we were able to distinguish cell binding avidity of tumor‐specific and non‐specific T cells. T cells engineered with a melanoma antigen‐specific T cell receptor showed a six‐fold increase in avidity relative to non‐specific T cells. In conclusion, we demonstrate a novel method to measure cell binding avidity with a high degree of specificity through the application of acoustic forces.