Immunotherapy of cancer using systemically delivered gene-modified human T lymphocytes

Human Gene Therapy
Michèle W L TengPhillip K Darcy

Abstract

The use of gene-engineered T cells expressing chimeric single-chain (scFv) receptors capable of codelivering CD28 costimulation and T cell receptor zeta chain (TCR-zeta) activation signals has emerged as a promising treatment regimen for cancer. Using retroviral transduction, primary human T lymphocytes were gene-engineered to express the scFv-CD28-zeta chimeric receptor reactive with the ErbB2 tumor-associated antigen. We demonstrated the ability of these gene-engineered human T cells to produce high levels of cytokines, proliferate vigorously, and mediate lysis of ErbB2(+) tumors in an antigen-specific manner. Furthermore, such gene-engineered human T cells significantly delayed the growth of two distinct subcutaneous ErbB2(+) human tumors in irradiated nonobese diabetic-severe combined immunodeficient (NOD-SCID) mice after systemic administration. These preclinical studies are an important proof of principle that human T cells may be genetically redirected to tumors in cancer patients.

References

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Citations

Apr 8, 2010·Archivum Immunologiae Et Therapiae Experimentalis·David Marc Davies, John Maher
Apr 25, 2012·Cancer Immunology, Immunotherapy : CII·Grazyna Lipowska-BhallaDominic G Rothwell
Sep 24, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xiao-Song ZhongMichel Sadelain
Oct 21, 2006·Human Gene Therapy·Michele W L TengPhillip K Darcy
Dec 21, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jennifer A WestwoodMichael H Kershaw
Apr 6, 2011·Expert Opinion on Biological Therapy·Carlos A Ramos, Gianpietro Dotti
Jun 13, 2015·Artificial Cells, Nanomedicine, and Biotechnology·Mostafa Haji-FatahalihaMehdi Yousefi
Mar 21, 2009·Alimentary Pharmacology & Therapeutics·R SrirajaskanthanM E Caplin
Jan 21, 2012·The Journal of Gene Medicine·Kevin J CurranRenier J Brentjens
Dec 18, 2013·Immunological Reviews·Gianpietro DottiMalcolm K Brenner
Apr 28, 2007·Cytotherapy·R Martiniello-Wilks, J E J Rasko
Dec 3, 2005·Nature Reviews. Immunology·Michael H KershawPhillip K Darcy
Jul 25, 2013·Nature Reviews. Cancer·Michael H KershawPhillip K Darcy
Jan 27, 2016·World Journal of Gastroenterology : WJG·Arvind GulbakeSanjay K Jain
Feb 4, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hao WangYajun Guo
Sep 15, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Renier J BrentjensMichel Sadelain
Jun 23, 2021·Future Oncology·Mighmig Simonian GharghaniBabak Negahdari

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