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Updated: Aug 2, 2026
A Preclinical Murine Model of Hepatic Metastases
Published on: September 27, 2014
Control of metastasized pancreatic carcinomas in SCID/beige mice with human IL-2/TKD-activated NK cells
Stefan Stangl1, Andreas Wortmann, Ulrich Guertler
1Department of Hematology and Oncology, University Hospital Regensburg, Franz-Josef Strauss Allee 11, 93053 Regensburg, Germany.
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.
Insights
Natural killer (NK) cells activated with low-dose interleukin-2 plus Hsp70-peptide (IL-2/TKD) effectively target pancreatic cancer. This immunotherapy eradicated tumors and prevented metastasis in a mouse model, offering a promising new treatment for Hsp70-positive pancreatic carcinoma.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Pancreatic carcinoma is a leading cause of cancer mortality.
- The stress-inducible heat shock protein 70 (Hsp70) is often present on the cell membrane of pancreatic cancer cells.
- Current treatment options for pancreatic cancer have limited efficacy.
Purpose of the Study:
- To investigate the efficacy of natural killer (NK) cells activated with low-dose interleukin-2 (IL-2) plus an Hsp70-peptide (TKD) in a xenograft pancreatic carcinoma model.
- To evaluate the therapeutic potential of this immunological approach against aggressive, Hsp70-positive pancreatic tumors and metastases.
Main Methods:
- Development of a xenograft pancreatic carcinoma model using Colo357 cells in SCID/beige mice.
- Activation of NK cells with either IL-2/TKD or IL-2 alone.
- In vitro assessment of NK cell lytic capacity against Hsp70-positive cancer cells.
- In vivo administration of activated NK cells via intravenous infusion.
- Monitoring of tumor growth, metastasis, and animal survival.
Main Results:
- IL-2/TKD-activated NK cells demonstrated enhanced lytic capacity against Hsp70-positive Colo357 cells in vitro.
- A single in vivo administration of IL-2/TKD-activated NK cells significantly reduced tumor weight, delayed hepatic metastases, and prolonged survival.
- Repeated infusions of IL-2/TKD-activated NK cells eradicated primary tumors and prevented hepatic metastases in mice.
- NK cells activated with IL-2 alone or T cells showed significantly less efficacy in controlling tumors and metastases.
Conclusions:
- Preactivation of NK cells with IL-2/TKD represents a potent strategy for targeting Hsp70-positive pancreatic carcinoma.
- This approach shows promise as a novel therapeutic tool for aggressive pancreatic cancers.
- Further research into IL-2/TKD-activated NK cell therapy is warranted for clinical translation.
