
The C-Trap® provides the world’s first dynamic single-molecule microscope to allow simultaneous manipulation and visualization of single-molecule interactions in real time.

Despite significant progress in haploidentical hematopoietic cell transplantation (haploHCT) for leukemia, relapse-free survival remains a major challenge, even with the addition of immune effectors such as NK or T cells. Given the crucial role of NK cells and their killer immunoglobulin receptors (KIRs) in early anti-leukemic activity, this study sought to refine the understanding of KIR:HLA (human leukocyte antigen) interactions in order to better predict patient outcomes.Using a combination of in silico protein folding and interaction modeling with in vitro acoustic force microscopy to quantify immune synapse avidity, Peter's group identified and validated a novel functional interaction between full-length KIR2DS4 and HLA-B*35. This interaction was confirmed through cell avidity assays with monoallelic KIR and HLA cell lines. When applied to clinical data, patients who received haploHCT and NK cell addback from donors expressing only full-length KIR2DS4 showed significantly improved overall and relapse-free survival. These findings were independently validated in an adult cohort, revealing consistent survival advantages.This newly defined KIR2DS4:HLA-B*35 axis represents an immediately actionable marker for donor selection and offers a mechanistic insight into optimizing NK cell-mediated anti-leukemic responses.
T cells play a pivotal role in tumor immunosurveillance. Multispecific cell engagers (CEs) have been adopted in the field of immuno-oncology to redirect T cells toward cancer cells, thereby unleashing the anti-tumor potential of the patient’s immune system. CE-mediated cell binding induces T cell activation and the formation of an immunological synapse, which is a prerequisite for effective tumor cell lysis.
The strength of the initial binding events between a T cell and a tumor cell dictates the efficiency of the anti-tumor response. Assessing cell avidity, i.e. the total intercellular interaction strength between two cells, gives crucial insights into the efficacy of CEs as anti-tumor therapeutic agents.
Here, we deploy LUMICKS’ high throughput avidity measurement (HTAM) technology to measure CE-induced cell avidity in a high throughput manner. We demonstrate the assay performance characteristics, i.e. specificity, precision, and range, via CE titration experiments in the context of a Jurkat T cell model system. We find that the HTAM CA assay is suitable for candidate screening in high throughput, with high sensitivity and precision.