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T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2011 Mar; Vol. 19 (3), pp. 620-6. Date of Electronic Publication: 2010 Dec 14. - Publication Year :
- 2011
-
Abstract
- Autologous T lymphocytes genetically engineered to express a murine T cell receptor (TCR) against human carcinoembryonic antigen (CEA) were administered to three patients with metastatic colorectal cancer refractory to standard treatments. All patients experienced profound decreases in serum CEA levels (74-99%), and one patient had an objective regression of cancer metastatic to the lung and liver. However, a severe transient inflammatory colitis that represented a dose limiting toxicity was induced in all three patients. This report represents the first example of objective regression of metastatic colorectal cancer mediated by adoptive T cell transfer and illustrates the successful use of a TCR, raised in human leukocyte antigen (HLA) transgenic mice, against a human tumor associated antigen. It also emphasizes the destructive power of small numbers of highly avid T cells and the limitations of using CEA as a target for cancer immunotherapy.
- Subjects :
- Adult
Animals
Carcinoembryonic Antigen blood
Colitis chemically induced
Colitis pathology
Colorectal Neoplasms diagnostic imaging
Colorectal Neoplasms pathology
Colorectal Neoplasms therapy
Gene Transfer Techniques
Genetic Vectors genetics
Genetic Vectors metabolism
Humans
Immunotherapy, Adoptive
Male
Mice
Middle Aged
Radiography
Receptors, Antigen, T-Cell genetics
Receptors, Antigen, T-Cell metabolism
Retroviridae genetics
Retroviridae metabolism
T-Lymphocytes metabolism
Treatment Outcome
Carcinoembryonic Antigen immunology
Colitis immunology
Colorectal Neoplasms immunology
Colorectal Neoplasms secondary
Receptors, Antigen, T-Cell immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 19
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 21157437
- Full Text :
- https://doi.org/10.1038/mt.2010.272