Antigen multimers: Specific, sensitive, precise, and multifunctional high-avidity CAR-staining reagents

Hu, Yifei; Cao, Guoshuai; Chen, Xiufen; Huang, Xiaodan; Asby, Nicholas; Ankenbruck, Nicholas; Rahman, Ali; Thusu, Ashima; He, Yonghui; Riedell, Peter A.; Bishop, Michael; Schreiber, Hans; Kline, Justin; Huang, Jun

doi:10.1016/j.matt.2021.09.027

Cited by 5 publications

(3 citation statements)

References 51 publications

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“…To this end, Jun Huang discussed his work on engineered chimeric antigen receptor T (CAR T) cells 17 . These cells have engineered specificity but must still be identified and isolated for single-cell analyses, requiring the use of novel multimer-based reagents for isolation and analysis.…”

Section: Meeting Reportmentioning

confidence: 99%

“…These multimer-based reagents include dodecamers that have higher sensitivity and better specificity compared to other reagents. They can be utilized for in vivo detection and activation of CAR T cells in individuals with cancers 17 . Furthermore, the engineered receptor generates a new range of potential cell states that may not always map effectively onto the endogenous cell states defined in infectious or even tumor-associated responses.…”

Section: Meeting Reportmentioning

confidence: 99%

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NIAID workshop on T cell technologies

et al. 2023

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Section: Meeting Reportmentioning

confidence: 99%

Section: Meeting Reportmentioning

confidence: 99%

NIAID workshop on T cell technologies

et al. 2023

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“…Despite the clinical importance of understanding antigen densities and the hundreds of new CAR designs and therapies for new target antigens and cancers being developed or undergoing clinical trials 47 , only a few options exist to assess antigen-density thresholds for CAR T cell responses, such as material-fixed antigens or antigen multimers 41,48,49 . Additionally, cell lines with varying antigen densities, which more closely imitate in vivo cell-to-cell interactions, are also used, albeit with a lack of orthogonality and limited control of antigen densities [32][33][34][35][36][37][38][39][40]50,51 .…”

Section: Introductionmentioning

confidence: 99%

Engineered yeast cells simulating CD19+ cancers to control CAR T cell activation

Deichmann,

Schiesaro,

Ramanathan

et al. 2023

Preprint

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Chimeric antigen receptor (CAR) T cells have become an established form of immunotherapy and continue to show promising results for the treatment of hematological cancers in most patients. While this immunotherapy continues to generate excitement in the clinic, antigen modulation in cancer cells affects the quality and safety of CAR T cell therapy. Here we present the engineering of yeast to robustly and dynamically modulate antigen densities, hence establishing a novel tool for assessing antigen-density thresholds in CAR T cell responses. Using a synthetic biology approach, we successfully engineer yeast to simulate cancer cells and demonstrate i) controllable antigen densities of CD19 through the use of G protein-coupled receptors (GPCRs), ii) a customizable system for tuning antigen densities through the employment of heterologous GPCRs for defining signal input types and signal pathway engineering for adapting intensities, and iii) activational control of clinically-derived CAR T cells within a physiologically relevant range compared to the activation elicited by a NALM6 cancer cell line. Based on this yeast-based antigen-presenting cell system, we envision an efficient assessment of how varying antigen densities in cancer cells from patients affect CAR T cell responses and ultimately support safer and better quality of personalized cancer therapies.

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