Potent induction of B- and T-cell immunity against human carcinoembryonic antigen-expressing tumors in human carcinoembryonic antigen transgenic mice mediated by direct lentivector injection. Mol Cancer Ther 2009 Mar;8(3):692-702
Date
03/12/2009Pubmed ID
19276164Pubmed Central ID
PMC2846382DOI
10.1158/1535-7163.MCT-08-0769Scopus ID
2-s2.0-66449130673 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
The applicability of immunotherapy would be dramatically broadened to a greater number of recipients if direct "off-the-shelf" products could be engineered to engender functionally potent immune responses against true "self"-tumor antigens. This would obviate the need for ex vivo culture of dendritic cells or T cells on a patient-by-patient basis, for example. The carcinoembryonic antigen (CEA) is a glycoprotein expressed in normal gut epithelium that is up-regulated in the majority of colon cancers, non-small cell lung cancers, and half of all breast cancers. Such properties make CEA an excellent and important target for cancer immunotherapy. In this study, we show stabilization of 14-day established s.c. mGC4CEA tumors in human CEA (huCEA) transgenic mice following two direct low-dose injections of 0.15x10(6) transducing units of a lentiviral vector (LV) that directs expression of huCEA (LV-huCEA). This stabilization result was reproducible and detailed analyses including antibody assays, multiplex cytokine analyses on unstimulated splenocytes, lymph node cell characterizations, tetramer staining, and immunofluorescence staining of tumor sections showed that this outcome correlated with both a cellular and humoral immune response. Similar tumor outcomes were not seen when mice were vaccinated with a control LV that engineered expression of enGFP only. The long-term potency of this vaccination strategy was also studied and revealed the requirement for maintenance of tumor antigen-specific immunity for efficient tumor control. These data support the use of direct injections of low doses of LV-huCEA for enhancement of tumor immunotherapy directed against CEA.
Author List
Loisel-Meyer S, Felizardo T, Mariotti J, Mossoba ME, Foley JE, Kammerer R, Mizue N, Keefe R, McCart JA, Zimmermann W, Dropulic B, Fowler DH, Medin JAAuthor
Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsB-Lymphocytes
Carcinoembryonic Antigen
Cells, Cultured
Genetic Therapy
Genetic Vectors
Humans
Immunity, Cellular
Immunotherapy
Injections
Lentivirus
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neoplasms
T-Lymphocytes
Tumor Burden
