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T cell-mediated delay of spontaneous mammary tumor onset: increased efficacy with in vivo versus in vitro activation.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2005 Apr 15; Vol. 174 (8), pp. 4662-9. - Publication Year :
- 2005
-
Abstract
- Peripheral tolerance to shared Ags expressed on both tumors and normal self-tissues presents a major barrier to T cell-based immunotherapy as a treatment for cancer. To assess the activity of tumor-specific T cells against spontaneously arising carcinomas in the context of shared Ag expression, we developed a model system whereby an identified tumor Ag, tumor ERK (tERK), is expressed transgenically on both normal mammary tissue and spontaneous mammary carcinomas. Transfer of in vitro-activated, tERK-specific DUC18 T cells delayed spontaneous tumor development in tERK-expressing mice when T cells were given before the development of palpable carcinomas. However, antitumor activity mediated by in vitro-activated DUC18 T cells, as measured by responsiveness against a transplanted tERK-expressing fibrosarcoma challenge, was lost within days of transfer. This loss was due to expression of tERK as a self-Ag on normal tissues and was independent of the presence of mammary tumors. In contrast, transferred naive DUC18 T cells maintained a long-term protective function in tERK-expressing mice. Ten-fold fewer naive T cells activated in vivo were able to replicate the delay in spontaneous tumor development achieved by in vitro-activated T cells. These results are in contrast to our earlier studies using transplanted tumors alone, in which in vitro-activated DUC18 T cells were more efficacious than naive DUC18 T cells and highlight the need to perform tumor studies in the presence of tumor Ag expression on normal self-tissue.
- Subjects :
- Animals
Antigens, Neoplasm
Autoantigens
Base Sequence
DNA, Recombinant genetics
Female
Immune Tolerance
Immunotherapy, Adoptive
In Vitro Techniques
Lymphocyte Activation
Mammary Neoplasms, Experimental therapy
Mice
Mice, Inbred BALB C
Mice, Transgenic
Mammary Neoplasms, Experimental etiology
Mammary Neoplasms, Experimental immunology
T-Lymphocytes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 0022-1767
- Volume :
- 174
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 15814690
- Full Text :
- https://doi.org/10.4049/jimmunol.174.8.4662