Immunotherapy with autologous tumor cells engineered to secrete Tag7/PGRP, an innate immunity recognition molecule
- 30 March 2004
- journal article
- research article
- Published by Wiley in The Journal of Gene Medicine
- Vol. 6 (7), 798-808
- https://doi.org/10.1002/jgm.560
Abstract
Background Recent studies indicate that the innate component of immune defense plays an important role in the establishment of antigen-specific immune response. We have previously isolated a novel mouse gene tag7/PGRP that was shown to be involved in the innate component of the immune system, and its insect homologue is an upstream mediator of Toll signaling in Drosophila. Methods Transiently or stably genetically modified mouse tumor cell lines expressing Tag7 were used. Tumor growth rate and animal survival were analyzed. Possible effector cells involved in tumor suppression were detected immunohistochemically. Results Transfection of mammary gland adenocarcinoma cells with the tag7 cDNA did not alter their growth rate in vitro but diminished their tumorogenicity in vivo in syngeneic and immunodeficient animals. Increased incidence of apoptosis was registered in the modified tumors. Transient expression of Tag7 by mouse melanoma M3 cells elicited protective immunity against parental tumor cells. Immunohistochemical analysis revealed that tumors after immunization with the genetically modified cells were infiltrated with Mac1+ cells, B220+ cells, and NK cells. Using nude mice we observed rejection of modified cells, but did not detect memory formation. Conclusions We can conclude that secretion of the Tag7 protein by genetically modified cells can induce mobilization of antigen-presenting cells and innate effectors. Memory mechanisms are mediated by T cell response. For the first time our results demonstrate that local secretion of Tag7—the molecule involved in innate immunity—may play an important role in the induction of effective antitumor response in mice. Copyright © 2004 John Wiley & Sons, Ltd.Keywords
This publication has 38 references indexed in Scilit:
- Isolation, Characterization, and Antimicrobial Properties of Bovine Oligosaccharide-binding ProteinPublished by Elsevier BV ,2002
- The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition proteinNature, 2002
- A subfraction of B220+ cells in murine bone marrow and spleen does not belong to the B cell lineage but has dendritic cell characteristicsEuropean Journal of Immunology, 2002
- Induction of tumor-specific T cell memory by NK cell–mediated tumor rejectionNature Immunology, 2001
- Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition proteinNature, 2001
- THE CLONING OF A RAT PEPTIDOGLYCAN RECOGNITION PROTEIN (PGRP) AND ITS INDUCTION IN BRAIN BY SLEEP DEPRIVATIONCytokine, 2001
- Genetic modification of a carcinoma with the IL‐4 gene increases the influx of dendritic cells relative to other cytokinesEuropean Journal of Immunology, 1997
- Phase I Study to the Immunotherapy of Metastatic Malignant Melanoma by a Cancer Vaccine Consisting of Autologous Cancer Cells Transfected with the Human IL-2 Gene. University of Vienna, AustriaHuman Gene Therapy, 1996
- Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now?Immunology Today, 1994
- Cytotoxic Cs in Immunodeficient Athymic MiceImmunopharmacology and Immunotoxicology, 1994