What is avidity and why is it important?
The missing parameter in immuno-oncology
In this post, we introduce the term “cell avidity”, and discuss what it is and how it fills the current scientific research gap
Binding events between a T cell and its target tumor cell determine the initiation of immunological synapse formation. This in turn sets a series of important events in motion, such as T-cell activation, T cell expansion, tumor cell elimination and persistence. These events are all a function of the signals provided upon that initial binding event. Cell–cell interactions are, therefore, crucial parameters to consider when trying to comprehend T cell response processes.
Cell avidity defines the total intercellular force between multiple parallel interactions, including co-receptor binding, TCR clustering, cell adhesion proteins, and even orientations and valencies. This sets it apart from affinity, as the latter only measures the binding strength between a single receptor-ligand pair. Furthermore, as the immune synapse can be seen as a communication between an immune and a tumor cell, where multiple cell-cell interactions happen in parallel, measuring cell avidity allows researchers to better understand this interface.
Compared with affinity, cell avidity provides a more complete and physiologically relevant picture that reflects the bona fide interaction between effector cells and tumor cells. These interactions serve to better predict cellular responses and outcomes during immunotherapy.
Researchers still face challenges to identify and validate effective cell-based therapies. Our understanding of the processes underlying patient’s response and toxicities is still incomplete. The approaches commonly used today to select the best immunotherapeutic effector cells include surface plasmon resonance (SPR) affinity studies, tetramer staining, and
Results from affinity and tetramer assays are inconsistent and do not correlate linearly with immune cell response. Functional assays, such as IFN-γ secretion and cell killing, are more predictive of effector response in vivo but are time-consuming and inconsistent between experiments or assays (Sibener et al., (2018) Cell; Zhang et al., (2016) Science Translational Medicine).
On the other hand, cell avidity analysis encompasses all synaptic interactions between the immune cell and target cell, and is therefore more predictive of T cell function. Recent studies assessing dual-targeted CAR T cell approaches have shown that cell avidity measurement better correlates with in vivo outcomes than traditional cell killing and EC50 assays (de Larrea et al., (2020) Blood Cancer Discovery).
The z-Movi® Cell Avidity Analyzer is a solution for researchers to determine cell avidity, which has been notoriously difficult to measure until now. Through avidity measurements, the z-Movi can help researchers investigating cell interaction properties that correspond to immune cell response in a predictive, reproducible, and fast manner. All this at a high-throughput and single-cell level, without compromising cell viability.
Being able to measure these interactions provides researchers valuable information and enables them to select best candidates at an early stage. This informed selection from the start can improve their success rate dramatically.