Extended Data Fig. 6: 80BB does not lead to by-stander cell activation nor increased CRS compared to a clinical-licensed CAR.
From: Synthetic dual co-stimulation increases the potency of HIT and TCR-targeted cell therapies
a, Representation of in vitro by-stander activation assay. Labelled 19-HIT T cells were plated onto wells with 19-HIT cells or 19-HIT80BB cells, or wells coated with CD28 superagonist antibody (CD28 SA) in the absence of target cells. b, c, Quantification of cell-surface CD69 on bystander 19-HIT cells (b) and levels of IL-2, IFNɣ and TNFα in the supernatant (c) 24hrs after exposure to wells containing 19-HIT, 19-HIT80BB or coated with CD28SA. n = 4 independent co-cultures of cells from a donor, representative of 2 donors. d, Left, Diagram depicting in vivo cytokine release syndrome (CRS) model. Right, weight change of tumour-bearing mice after 19-HIT (n = 8 mice), 19-HIT80BB (n = 4 mice), 1928z CAR (n = 6 mice) or no (n = 4 mice) T cell transfer. Weight per mouse is normalized to starting weight before T cell infusion. 10% cut-off for CRS is illustrated with a dotted line. e, f, Frequency of diarrhea in days (e) and serum cytokine levels 18hrs (f) after T cell infusion into tumour-bearing Scid Beige mice. P values were determined by two-tailed t-test (b, c, f) and Chi-square test(e). Data are mean ± sem.
