title: Plasma IFN-γ and IL-6 levels correlate with peripheral T-cell numbers but not toxicity in RCC patients treated with CAR T-cells.
abstract: Autologous T-cells genetically modified to express a chimeric antigen receptor (CAR) against carboxy-anhydrase-IX (CAIX) were administered to twelve patients with CAIX-positive metastatic renal cell carcinoma. Here, we questioned whether plasma cytokine levels following treatment or in vitro cytokine production from the T-cell infusion products could serve as predictors for peripheral T-cell persistence or in vivo T-cell activity. We demonstrated that CAR surface as well as gene expression are down-regulated following T-cell infusion, and that peripheral numbers of CAR T-cells are best captured by flow cytometry and not by qPCR. Numbers of CAR T-cells in blood correlated with plasma levels of IFN-γ and IL-6, but not with any of the other cytokines tested. Plasma IFN-γ or IL-6 levels did not correlate with liver enzyme values. Thus, out of 27 cytokines tested, IFN-γ and IL-6 levels in plasma are potential surrogate markers for CAR T-cell persistence in solid tumors.
authors.affiliation: Laboratory of Tumor Immunology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Yarne
authors.initials: Y
authors.lastname: Klaver
authors.affiliation: Laboratory of Tumor Immunology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Sabine C L
authors.initials: SCL
authors.lastname: van Steenbergen
authors.affiliation: Department of Medical Oncology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
authors.affiliation: Laboratory of Tumor Immunology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Reno
authors.initials: R
authors.lastname: Debets
authors.affiliation: Laboratory of Tumor Immunology, Erasmus MC-Cancer Institute, Rotterdam, The Netherlands. Electronic address: c.lamers@erasmusmc.nl.
authors.forename: Cor H J
authors.initials: CHJ
authors.lastname: Lamers
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000276:immunology; D002292:Carcinoma, Renal Cell / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D016207:Cytokines / Q000097:blood / Q000276:immunology; D005434:Flow Cytometry; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology*; D007680:Kidney Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D018655:Lymphocyte Count; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013997:Time Factors
chemical_list: D014408:Biomarkers, Tumor; D016207:Cytokines; D015850:Interleukin-6; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D007371:Interferon-gamma
keywords: Chimeric antigen receptor; Cytokines; IFN-γ; Immune monitoring; Renal cell cancer; T-cell