Alzubi, Jamal and Dettmer-Monaco, Viviane and Kuehle, Johannes and Thorausch, Niko and Seidl, Maximilian and Taromi, Sanaz and Schamel, Wolfgang and Zeiser, Robert and Abken, Hinrich and Cathomen, Toni and Wolf, Philipp (2020) PSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model. MOLECULAR THERAPY-ONCOLYTICS, 18. pp. 226-235. ISSN 2372-7705,
Full text not available from this repository. (Request a copy)Abstract
While chimeric antigen receptor (CAR) T cell immunotherapy targeting CD19 has shown remarkable success in patients with lymphoid malignancies, the potency of CAR T cells in solid tumors is low so far. To improve the efficacy of CAR T cells targeting prostate carcinoma, we designed a novel CAR that recognizes a new epitope in the prostate-specific membrane antigen (PSMA) and established novel paradigms to apply CAR T cells in a preclinical prostate cancer model. In vitro characterization of the D7 single-chain antibody fragment-derived anti-PSMA CAR confirmed that the choice of the co-stimulatory domain is a major determinant of CART cell activation, differentiation, and exhaustion. In vivo, focal injections of the PSMA CAR T cells eradicated established human prostate cancer xenografts in a preclinical mouse model. Moreover, systemic intravenous CAR T cell application significantly inhibited tumor growth in combination with non-ablative low-dose docetaxel chemotherapy, while docetaxel or CAR T cell application alone was not effective. In conclusion, the focal application of D7-derived CAR T cells and their combination with chemotherapy represent promising immunotherapeutic avenues to treat local and advanced prostate cancer in the clinic.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHIMERIC ANTIGEN RECEPTORS; MEMBRANE ANTIGEN; IN-VITRO; EXPRESSION; GENOME; TARGET; IMMUNOTOXIN; ACTIVATION; DIAGNOSIS; THERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 11 Mar 2021 08:30 |
| Last Modified: | 11 Mar 2021 08:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43757 |
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