Journal: Med (New York, N.Y.)
Article Title: A chimeric antigen receptor uniquely recognizing MICA/B stress proteins provides an effective approach to target solid tumors.
doi: 10.1016/j.medj.2023.04.004
Figure Lengend Snippet: Figure 1. 3MICA/B CAR targets the conserved alpha-3 domains of MICA/B stress ligands and is resistant to binding competition by shed MICA/B A novel MICA/B-targeting synthetic receptor capable of high-affinity pan-allelic binding, surface MICA/B density augmentation, and resistance to inhibition via shed MICA and MICB peptides. (A) Domain-specific amino acid sequence similarity was scored across the 21 most prevalent MICA and MICB alleles using the BLOSUM method highlighting greater sequence conservation within the membrane-proximal a3 domain relative to the membrane-distal a1-2 domains. (B) Pan-allelic reactivity of 3MICA/B mAb, an a1-2 MICA/B-reactive mAb (6D4), and NKG2D:Fc fusion protein was assessed across an extended panel of 28 prevalent MICA alleles. (C) MM1-R cells, pre-treated with trypsin to cleave baseline surface-expressed MICA/B ligands, were incubated with 3MICA/B mAb, or relevant isotype, and surface MICA/B expression kinetics was measured using a commercial mAb (6D4) over a 96-h time course. In parallel, MM1.R cells were incubated
Article Snippet: The concentration of shed MICA/B was measured using a human MICA ELISA (Ab59569, Abcam) or human MICB DuoSet ELISA kit (DY1599, R&D Systems), following the manufacture’s recommendation.
Techniques: Binding Assay, Inhibition, Sequencing, Membrane, Incubation, Expressing