The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
A Novel Chimeric Antigen Receptor Against Prostate Stem Cell Antigen Mediates Tumor Destruction in a Humanized Mouse Model of Pancreatic Cancer
Open accessAbstract
Despite advances in the understanding of its molecular pathophysiology, pancreatic cancer remains largely incurable, highlighting the need for novel therapies. We developed a chimeric antigen receptor (CAR) specific for prostate stem cell antigen (PSCA), a glycoprotein that is overexpressed in pancreatic cancer starting at early stages of malignant transformation. To optimize the CAR design, we used antigen-recognition domains derived from mouse or human antibodies, and intracellular signaling domains containing one or two T cell costimulatory elements, in addition to CD3zeta. Comparing multiple constructs established that the CAR based on human monoclonal antibody Ha1-4.117 had the greatest reactivity in vitro. To further analyze this CAR, we developed a human pancreatic cancer xenograft model and adoptively transferred CAR-engineered T cells into animals with established tumors. CAR-engineered human lymphocytes induced significant antitumor activity, and unlike what has been described for other CARs, a second-generation CAR (containing CD28 cosignaling domain) induced a more potent antitumor effect than a third-generation CAR (containing CD28 and 41BB cosignaling domains). While our results provide evidence to support PSCA as a target antigen for CAR-based immunotherapy of pancreatic cancer, the expression of PSCA on selected normal tissues could be a source of limiting toxicity.
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Cites
Siegel, R., Naishadham, D., & Jemal, A. (2012) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20138 · Cited by 10,679
A human memory T cell subset with stem cell–like properties
Gattinoni, L., Lugli, E., Ji, Y., Pos, Z., Paulos, C. M., Quigley, M. F., Almeida, J. R., Gostick, E., Yu, Z., Carpenito, C., et al. (2011) · Nature Medicine · doi:10.1038/nm.2446 · Cited by 1,974 · cited 1×
“Transduced lymphocytes were administered together with untransduced CD4 + cells to provide homeostatic cytokines as previously described (Gattinoni et al., 2011).”
MethodSelf-citationInducible Apoptosis as a Safety Switch for Adoptive Cell Therapy
Di Stasi, A., Tey, S.-K., Dotti, G., Fujita, Y., Kennedy-Nasser, A., Martinez, C., Straathof, K., Liu, E., Durett, A. G., Grilley, B., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1106152 · Cited by 1,512
Molecular genetics of pancreatic intraepithelial neoplasia
Feldmann, G., Beaty, R., Hruban, R. H., & Maitra, A. (2007) · Journal of Hepato-Biliary-Pancreatic Surgery · doi:10.1007/s00534-006-1166-5 · Cited by 269
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CAR-T cell therapy: current limitations and potential strategies
Sterner, R. C., & Sterner, R. M. (2021) · Blood Cancer Journal · doi:10.1038/s41408-021-00459-7 · Cited by 2,926
Toxicities of chimeric antigen receptor T cells: recognition and management
Brudno, J. N., & Kochenderfer, J. N. (2016) · Blood · doi:10.1182/blood-2016-04-703751 · Cited by 1,283
Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition
Ren, J., Liu, X., Fang, C., Jiang, S., June, C. H., & Zhao, Y. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-16-1300 · Cited by 942
In situ programming of leukaemia-specific T cells using synthetic DNA nanocarriers
Smith, T. T., Stephan, S. B., Moffett, H. F., McKnight, L. E., Ji, W., Reiman, D., Bonagofski, E., Wohlfahrt, M. E., Pillai, S. P. S., & Stephan, M. T. (2017) · Nature Nanotechnology · doi:10.1038/nnano.2017.57 · Cited by 785
Stromal biology and therapy in pancreatic cancer: ready for clinical translation?
Neesse, A., Bauer, C. A., Öhlund, D., Lauth, M., Buchholz, M., Michl, P., Tuveson, D. A., & Gress, T. M. (2019) · Gut · doi:10.1136/gutjnl-2018-316451 · Cited by 353
Metadata
- Authors
- Abate-Daga, D., Lagisetty, K. H., Tran, E., Zheng, Z., Gattinoni, L., Yu, Z., Burns, W. R., Miermont, A. M., Teper, Y., Rudloff, U., Restifo, N. P., Feldman, S. A., Rosenberg, S. A., & Morgan, R. A.
- Venue
- Human Gene Therapy
- Publisher
- SAGE Publications
- Published
- 2014-12
- Volume
- 25
- Issue
- 12
- Pages
- 1003-1012
- ISSN
- 1043-0342 (ISSN-L)
- 1557-7422
- OpenAlex
- W1993778590
- Cited by
- 191
- References
- 4
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Abate-Daga, D., Lagisetty, K. H., Tran, E., Zheng, Z., Gattinoni, L., Yu, Z., Burns, W. R., Miermont, A. M., Teper, Y., Rudloff, U., Restifo, N. P., Feldman, S. A., Rosenberg, S. A., & Morgan, R. A. (2014). A Novel Chimeric Antigen Receptor Against Prostate Stem Cell Antigen Mediates Tumor Destruction in a Humanized Mouse Model of Pancreatic Cancer. Human Gene Therapy. https://doi.org/10.1089/hum.2013.209
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
