| Abstract: |
Gene-engineered T cell therapy represents a promising strategy to treat cancers. To enable pre-selection of patients sensitive to this type of treatment we have setup and validated a T cell activation assay to test antigen expression on patient-derived tumor tissues. Chimeric antibody-based receptor (CAR) directed against CAIX, currently used in a clinical trial to treat RCC patients, was used as a model receptor. Primary human T cells expressing CAIX CAR were able to respond to CAIX-positive but not CAIX-negative tumor tissue and showed an increased production of IFNγ, TNFα, IL-10 and IL-4, but not IL-2 or IL-5. Tumor tissue driven responses of primary T cells were paralleled by NFAT activation measured in CAR-transduced Jurkat T cells, which was shown to be triggered in a CAR and antigen-specific manner. Next, the reporter gene assay was applied to two independent PSMA CARs, which both mediated NFAT activation in response to tumor tissue. Taken together, a sensitive and donor-independent assay was established to measure T cell activation upon exposure to patient-derived tumor tissue, which may facilitate pre-selection of patients for clinical adoptive T cell therapy. © 2010 Elsevier B.V. |
| Keywords: |
immunohistochemistry; signal transduction; controlled study; human tissue; unclassified drug; human cell; clinical trial; histopathology; patient selection; antigen expression; t lymphocyte; t-lymphocytes; interleukin 2; interleukin 10; interleukin 4; interleukin 5; tumor cells, cultured; cell assay; kidney carcinoma; kidney neoplasms; prostate cancer; lymphocyte activation; prostate specific membrane antigen; antigen; tumor necrosis factor alpha; antigens, neoplasm; carbonate dehydratase ix; gamma interferon; genetic engineering; carcinoma, renal cell; antigen specificity; receptors, antigen, t-cell; gene therapy; reporter gene; cell therapy; adoptive transfer; cytokine production; cancer tissue; t lymphocyte activation; transcription factor nfat; leukemia cell line; jurkat cells; carbonic anhydrases; antigen-antibody reactions; chimeric antibody; chimeric antibody-based receptor (car); gene-modified t cells; nfat reporter gene assay; t cell therapy; chimeric antibody based receptor; adoptive t lymphocyte therapy
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