Control of Metastasized Pancreatic Carcinomas in Scid/Beige Mice with Human Il-2/Tkd-activated Nk Cells.
From: Department of Hematology and Oncology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93053 Regensburg, Germany.
Journal of immunology (Baltimore, Md. : 1950)
- Publish Date: May 2006
- ISSN: 0022-1767
- Volume: 176
- Issue: 10
- Pages: 6270-6
- Medium: Print
- Language: English
- Citation (JAMA): Stangl Stefan, Wortmann Andreas, Guertler Ulrich, et al. Control of Metastasized Pancreatic Carcinomas in Scid/Beige Mice with Human Il-2/Tkd-activated Nk Cells.. J. Immunol. May 2006;176:6270-6
Abstract
Pancreatic carcinoma, the fifth leading cause of cancer-related mortality, frequently presents the stress-inducible heat shock protein 70 (Hsp70) on the cell membrane. Therefore, we explored an immunological approach exploiting the efficacy of NK cells activated either with low dose IL-2 plus Hsp70-peptide TKDNNLLGRFELSG (TKD; IL-2/TKD) or with IL-2 alone in a xenograft pancreatic carcinoma model. An orthotopic injection of either 2.5 x 10(6) or 1 x 10(6) Colo357 cells in SCID/beige mice resulted in rapidly growing primary tumors and the development of hepatic metastases on days 5 and 10, respectively. In line with results of in vitro migration assays, these NK cells also had the capacity to infiltrate pancreatic tumors and liver metastases in tumor-bearing mice. In vitro, a combined treatment of NK cells with IL-2/TKD but neither of the two treatments alone causes a profound increase in the lytic capacity against Hsp70 membrane-positive Colo357 cells. In vivo, a single i.v. injection of these NK cells on day 15 post-tumor inoculation resulted in a significant reduction in tumor weights, a delayed onset of hepatic metastases, and a prolonged life expectancy. In contrast, identically treated T cells and NK cells treated with IL-2 alone were significantly less efficient in controlling pancreatic tumors and metastases. Most importantly, four repeated i.v. infusions of IL-2/TKD-activated NK cells eradicated primary tumors and prevented hepatic metastases. In summary, our mouse data have implicated that NK cells preactivated with IL-2/TKD might provide a novel therapeutic tool for the treatment of aggressive, Hsp70-positive pancreatic carcinoma.
Mesh Headings (Keywords): Adenocarcinoma, Adoptive Transfer, Animals, Cell Line, Tumor, Cell Movement, Female, HSP70 Heat-Shock Proteins, Humans, Interleukin-2, Killer Cells, Natural, Liver Neoplasms, Experimental, Lymphocyte Activation, Male, Mice, Mice, SCID, Neoplasm Transplantation, Pancreatic Neoplasms, Transplantation, Heterologous
Check for Full Text / PubMed Unique Identifier (PMID): 16670338
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.