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Background Antigen-specific T cells play a central role in the immune response against cancer. Precise identification and characterization of antigen-specific T cell receptors (TCRs) and their cognate peptide epitopes are critical for selecting candidates for TCR-based therapies and for monitoring T cell-mediated immune responses in patients. Given the highly individualized nature of antigen-specific T cell responses—shaped by the genetic diversity of the major histocompatibility complex—flexible and reliable TCR detection reagents are of utmost importance for successful therapy developments.Methods We have developed a novel MHC multimer technology, the MHC MACSimers, with optimized construct stability and binding avidity, to support TCR-based cell therapy workflows across all stages—from early discovery and epitope screening, to in-process and quality control (IPC/QC), as well as patient monitoring and translational research. To ensure seamless integration into diverse cancer drug development pipelines, MHC MACSimer reagents feature the following technical specifications:1. High flexibility through peptide-loading technology, enabling rapid and straightforward epitope screening during TCR discovery.2. Broad compatibility with up- and downstream applications, including magnetic cell separation, flow cytometry-based sorting, and multicolor flow cytometry for comprehensive T cell profiling.3. REAlease® technology for removal of the peptide-MHC staining post-flow sorting, facilitating downstream assays.4. An expanding portfolio of peptide-loaded multimers for standardized results in IPC/QC, such as measuring transduction efficiency of engineered T cell products.Results In this poster we demonstrate that MHC MACSimers enable sensitive detection of rare antigen-specific T cells, yielding stronger fluorescence signals compared to conventional MHC tetramers ( figure 1). We further show that MHC MACSimers facilitate the isolation and enrichment of peptide-MHC (pMHC)-specific T cell populations for downstream analyses. Besides, we demonstrate that MHC MACSimers seamlessly integrate into TCR discovery and engineered T cell manufacturing workflows, e.g., by reliable detection of TCR-transduced T cells (figure 2).Conclusions MHC MACSimers are optimized MHC multimers, enabling robust T cell analytics along the different stages of TCR-based therapy developments. They cover the need for product quality, flexibility, and data reproducibility, making them an ideal tool to integrate into cancer immunotherapy workflows.Abstract 367 Figure 1Detection of antigen-specific T cells using MHC MACSimers as compared to conventional MHC Tetramers.HLA-A*0101-positive Cytomegalovirus (CMV) pp50 antigen (VTEHDTLLY)-reactive CD8+ T cells were stained in parallel using conventional MHC tetramers (biotinylated MHC monomers multimerized on streptavidin) and MHC MACSimers (optimized MHC technology)Abstract 367 Figure 2Analysis of TCR-transduction efficiency in human engineered TCR-T cells using MHC MACSimers. HLA-A*0201-positive NY-ESO1- or MAGE-A4-specific TCR-T cells were generated with a TCT small-scale process using the CliniMACS® Prodigy platform. TCR-transduction rates were assessed by flow cytometry using MHC MACSimers