Fig. 7: HER2 CAR T-cell infusions after bone marrow relapse and monitoring during the second remission. | Nature Communications

Fig. 7: HER2 CAR T-cell infusions after bone marrow relapse and monitoring during the second remission.

From: Tumor response and endogenous immune reactivity after administration of HER2 CAR T cells in a child with metastatic rhabdomyosarcoma

Fig. 7: HER2 CAR T-cell infusions after bone marrow relapse and monitoring during the second remission.

a Surveillance bone marrow (BM) at 6 months after stopping HER2 CAR T-cell infusions showing hypocellularity and presence of HER2-expressing RMS cells (grade 2, intensity score 2+ by immunohistochemistry). b BM showing restoration of trilineage hematopoiesis and no morphological evidence of RMS (CR2) 6 weeks after one cycle of lymphodepletion and HER2 CAR T cells (1 × 108 cells/m2). Panels (a, b) show representative microscopic images; scale bar 100 µm. c Kinetics of serum IL-15 levels before and after HER2 CAR T-cell infusions given with Cy/Fly lymphodepletion (n = 3 infusion cycles). d HER2 CAR expression in the second autologous T-cell product manufactured and infused during consolidation of CR2. e Timeline of the initial treatment course, disease relapse, re-induction of CR2, and consolidation of the response shown in a schematic diagram. PD-1 antibody, pembrolizumab, was initiated 4 weeks after confirming the CR2 and continued every 3 weeks thereafter. f Analysis of pro-inflammatory cytokines (IFN-γ, TNFα, and GM-CSF) in the patient’s serum before and after CAR T-cell infusion given with (n = 3 infusion cycles) and without (n = 2 infusions) lymphodepletion. g Longitudinal monitoring of serum IL-6 and IL-4 levels during CR2, before and after adding PD-1-blocking antibody to the CAR T-cell infusion regimen, in comparison to CR1. Solid lines represent the mean values of sample duplicates tested. h Trends in the absolute lymphocyte count (ALC; shaded gray area) and levels of the HER2 CAR transgene detected by quantitative polymerase chain reaction (qPCR; solid black line) in the peripheral blood during the treatment phase of CR2 and the follow-up period. i Detection of HER2 CAR transgene in the matched BM and peripheral blood samples at 6 weeks after T-cell infusions during CR2. In panels (c, f), each dot in the graph represents an average of technical replicates from a biologically distinct serum sample. H&E hematoxylin and eosin stain, Cy/Flu cyclophosphamide and fludarabine.

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