0013105 2021 RIV GB eng J
Štach, Martin - Ptáčková, Pavlína - Mucha, Martin - Musil, Jan - Klener, P. - Otáhal, Pavel^G
Inducible secretion of IL-21 augments anti-tumor activity of piggyBac-manufactured chimeric antigen receptor T cells.
Cytotherapy. Vol. 22, no. 12 (2020), s. 744-754. ISSN 1465-3249
Grant: Ministerstvo zdravotnictví NV15-34498A
Klíčová slova: CAR T cells * chronic lymphocytic leukemia * interleukin 21 * piggyBac transposon
Cite Score: 7.600, rok: 2020; SJR: 1.192, rok: 2020; IF: 5.414, rok: 2020
DOI: 10.1016/j.jcyt.2020.08.005

Anotace: The efficiency of chimeric antigen receptor (CAR) T-cell-based therapies depends on a sufficient expansion of CAR T cells in vivo and can be weakened by intra-tumoral suppression of CAR T cell functions, leading to a failure of therapy. For example, certain B-cell malignancies such as chronic lymphocytic leukemia are weakly sensitive to treatment with CAR T cells. Co-expression of proinflamatory cytokines such as IL-12 and IL-18 by CAR T cells have been shown to enhance their antitumor function. We similarly engineered CAR T cell to co-express IL-21 and studied the effects of IL-21 on CAR T cells specific to CD19 and prostate-specific membrane antigens using an in vitro co-culture model and NSG mice transplanted with B-cell tumors.