The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety
Open accessAbstract
T lymphocytes expressing a chimeric antigen receptor (CAR) targeting the CD19 antigen (CAR.19) may be of value for the therapy of B-cell malignancies. Because the in vivo survival, expansion and anti-lymphoma activity of CAR.19+ T cells remain suboptimal even when the CAR contains a CD28 costimulatory endodomain, we generated a novel construct that also incorporates the interleukin-15 (IL-15) gene and an inducible caspase-9-based suicide gene (iC9/CAR.19/IL-15). We found that compared with CAR.19+ T cells, iC9/CAR.19/IL-15+ T cells had: (1) greater numeric expansion upon antigen stimulation (10-fold greater expansion in vitro, and 3- to 15-fold greater expansion in vivo) and reduced cell death rate (Annexin-V+/7-AAD+ cells 10±6% for iC9/CAR.19/IL-15+ T cells and 32±19% for CAR.19+ T cells); (2) reduced expression of the programmed death 1 (PD-1) receptor upon antigen stimulation (PD-1+ cells <15% for iC9/CAR.19/IL-15+ T cells versus >40% for CAR.19+ T cells); and (3) improved antitumor effects in vivo (from 4.7- to 5.4-fold reduced tumor growth). In addition, iC9/CAR.19/IL-15+ T cells were efficiently eliminated upon pharmacologic activation of the suicide gene. In summary, this strategy safely increases the anti-lymphoma/leukemia effects of CAR.19-redirected T lymphocytes and may be a useful approach for treatment of patients with B-cell malignancies.
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Cites
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Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors
Liu, E., Marin, D., Banerjee, P., Macapinlac, H. A., Thompson, P., Basar, R., Nassif Kerbauy, L., Overman, B., Thall, P., Kaplan, M., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa1910607 · Cited by 2,217
The future of cancer treatment: immunomodulation, CARs and combination immunotherapy
Khalil, D. N., Smith, E. L., Brentjens, R. J., & Wolchok, J. D. (2016) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2016.25 · Cited by 929
Global Manufacturing of CAR T Cell Therapy
Levine, B. L., Miskin, J., Wonnacott, K., & Keir, C. (2017) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2016.12.006 · Cited by 765
Kochenderfer, J. N., Somerville, R. P. T., Lu, T., Shi, V., Bot, A., Rossi, J., Xue, A., Goff, S. L., Yang, J. C., Sherry, R. M., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.3024 · Cited by 569
Interleukin 12: still a promising candidate for tumor immunotherapy?
Lasek, W., Zagożdżon, R., & Jakobisiak, M. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-014-1523-1 · Cited by 495
Metadata
- Authors
- Hoyos, V, Savoldo, B., Quintarelli, C., Mahendravada, A., Zhang, M., Vera, J., Heslop, H. E., Rooney, C. M., Brenner, M. K., & Dotti, G.
- Venue
- Leukemia
- Published
- 2010-04-29
- Volume
- 24
- Issue
- 6
- Pages
- 1160-1170
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- OpenAlex
- W2003197307
- Cited by
- 567
- References
- 48
- FWCI
- 9.83
- Type
- journal article
- Language
- en
- Open access
- green
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- Hoyos, V, Savoldo, B., Quintarelli, C., Mahendravada, A., Zhang, M., Vera, J., Heslop, H. E., Rooney, C. M., Brenner, M. K., & Dotti, G. (2010). Engineering CD19-specific T lymphocytes with interleukin-15 and a suicide gene to enhance their anti-lymphoma/leukemia effects and safety. Leukemia. https://doi.org/10.1038/leu.2010.75
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