Universität zu Köln

Alzubi, Jamal, Dettmer-Monaco, Viviane, Kuehle, Johannes, Thorausch, Niko, Seidl, Maximilian, Taromi, Sanaz, Schamel, Wolfgang, Zeiser, Robert, Abken, Hinrich, Cathomen, Toni ORCID: 0000-0002-7757-4630 and Wolf, Philipp (2020). PSMA-Directed CAR T Cells Combined with Low-Dose Docetaxel Treatment Induce Tumor Regression in a Prostate Cancer Xenograft Model. Mol. Ther.-Oncolytics, 18. S. 226 - 236. CAMBRIDGE: CELL PRESS. ISSN 2372-7705

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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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Alzubi, Jamal UNSPECIFIED UNSPECIFIED UNSPECIFIED Dettmer-Monaco, Viviane UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuehle, Johannes UNSPECIFIED UNSPECIFIED UNSPECIFIED Thorausch, Niko UNSPECIFIED UNSPECIFIED UNSPECIFIED Seidl, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Taromi, Sanaz UNSPECIFIED UNSPECIFIED UNSPECIFIED Schamel, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeiser, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Cathomen, Toni UNSPECIFIED orcid.org/0000-0002-7757-4630 UNSPECIFIED Wolf, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-318289
DOI:	10.1016/j.omto.2020.06.014
Journal or Publication Title:	Mol. Ther.-Oncolytics
Volume:	18
Page Range:	S. 226 - 236
Date:	2020
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2372-7705
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHIMERIC ANTIGEN RECEPTORS; MEMBRANE ANTIGEN; IN-VITRO; EXPRESSION; GENOME; TARGET; IMMUNOTOXIN; ACTIVATION; DIAGNOSIS; THERAPY Multiple languages Oncology; Medicine, Research & Experimental Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/31828