Plasma IFN-gamma and IL-6 levels correlate with peripheral T-cell numbers but not toxicity in RCC patients treated with CAR T-cells
| Autor: | Reno Debets, Cor H. J. Lamers, Stefan Sleijfer, Sabine C. L. van Steenbergen, Yarne Klaver |
|---|---|
| Přispěvatelé: | Medical Oncology |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Time Factors Recombinant Fusion Proteins T-Lymphocytes medicine.medical_treatment T cell Immunology Receptors Antigen T-Cell Biology Immunotherapy Adoptive Flow cytometry Interferon-gamma 03 medical and health sciences 0302 clinical medicine In vivo Biomarkers Tumor medicine Humans Immunology and Allergy Interferon gamma Lymphocyte Count Interleukin 6 Carcinoma Renal Cell medicine.diagnostic_test Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction Flow Cytometry Kidney Neoplasms Chimeric antigen receptor 030104 developmental biology Cytokine medicine.anatomical_structure 030220 oncology & carcinogenesis Toxicity biology.protein Cytokines medicine.drug |
| Zdroj: | Clinical Immunology, 169, 107-113. Academic Press |
| ISSN: | 1521-7035 1521-6616 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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