Publication Date:
2006-09-02
Description:
Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267026/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2267026/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Morgan, Richard A -- Dudley, Mark E -- Wunderlich, John R -- Hughes, Marybeth S -- Yang, James C -- Sherry, Richard M -- Royal, Richard E -- Topalian, Suzanne L -- Kammula, Udai S -- Restifo, Nicholas P -- Zheng, Zhili -- Nahvi, Azam -- de Vries, Christiaan R -- Rogers-Freezer, Linda J -- Mavroukakis, Sharon A -- Rosenberg, Steven A -- Z01 BC010763-01/Intramural NIH HHS/ -- Z01 SC003811-32/Intramural NIH HHS/ -- Z99 CA999999/Intramural NIH HHS/ -- New York, N.Y. -- Science. 2006 Oct 6;314(5796):126-9. Epub 2006 Aug 31.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/16946036" target="_blank"〉PubMed〈/a〉
Keywords:
*Adoptive Transfer
;
Adult
;
Antigens, Neoplasm/*immunology
;
CD8-Positive T-Lymphocytes/*immunology
;
Cancer Vaccines/therapeutic use
;
Cells, Cultured
;
Electroporation
;
Female
;
Genetic Engineering
;
*Genetic Therapy
;
HLA-A Antigens/immunology
;
HLA-A2 Antigen
;
Humans
;
Interleukin-2/immunology/therapeutic use
;
MART-1 Antigen
;
Male
;
Melanoma/immunology/secondary/*therapy
;
Middle Aged
;
Neoplasm Proteins/*immunology
;
Receptors, Antigen, T-Cell, alpha-beta/*genetics/*immunology
;
Transduction, Genetic
;
Transgenes
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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