T cell activation upon exposure to patient-derived tumor tissue: a functional assay to select patients for adoptive T cell therapy.

Autor: Schroten C; Dept Urology, Erasmus MC, Rotterdam, The Netherlands., Kraaij R, Veldhoven JL, Berrevoets CA, den Bakker MA, Ma Q, Sadelain M, Bangma CH, Willemsen RA, Debets R
Jazyk: angličtina
Zdroj: Journal of immunological methods [J Immunol Methods] 2010 Jul 31; Vol. 359 (1-2), pp. 11-20. Date of Electronic Publication: 2010 May 09.
DOI: 10.1016/j.jim.2010.04.006
Abstrakt: 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 IFNgamma, TNFalpha, 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. All rights reserved.)
Databáze: MEDLINE
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