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Breast Cancer Research and Treatment

, Volume 31, Issue 2–3, pp 349–356 | Cite as

Breast cancer gene therapy: transgenic immunotherapy

  • Ning Su
  • John O. Ojeifo
  • Alexander MacPherson
  • James A. Zwiebel
Article

Summary

A number of studies have demonstrated that potent anti-tumor immunity can be induced using cytokine gene transfer, a strategy termed transgenic immunotherapy. Our aim is to express cytokine genes in the vicinity of tumor cells, either by transducing tumor cells themselves, or by delivering cytokine-expressing endothelial cells to tumor sites. We compared the ability of cytokine-expressing tumor cells or endothelial cells to inhibit the tumorigenesis of MDA-MB-435 breast cancer cells in athymic nude mice. Retroviral vectors containing either human interleukin 2 (hIL-2) or interleukin 1 (hIL-1α) were used to transduce MDA-MB-435 cells or human umbilical vein endothelial cells (HUVEC). Using a modified MTT bioassay and an ELISA specific for hIL-2, 43 of 70 MDA-MB-435 clones transduced with IL-2 were found to secrete between 100–800 units of IL-2/106 cells/24 hr. hIL-2 and hIL-1α-transduced HUVEC secreted 40 ng/IL-2/106/24 hr and 1.8 ng/106/24 hr, respectively. To facilitatein vivo tracking of tumor cells, both nontransduced and IL-2-expressing MDA-MB-435 cells were genetically-marked with the E. colilacZ gene and selected using flow cytometry. To studyin vivo tumorigenicity, cells were injected into the mammary fat pad of athymic nude mice: (1)lacZ/MDA-MB-435 cells injected alone formed tumors in all animals ;(2) IL-2-expressinglacZ/MDA-MB-435 cells did not form any tumors; (3) co-inoculation of MDA-MB-435/IL-2, HUVEC/IL-2, or HUVEC/IL-1α withlacZ/MDA-MB-435 cells prevented or delayed tumor growth. These results suggest that local cytokine secretion was capable of activating natural killer cell activity in host animals. Transgenic immunotherapy is a promising approach that may be useful for the eradication of minimal residual disease.

Keywords

Breast Cancer Natural Killer Cell Human Umbilical Vein Endothelial Cell Minimal Residual Disease Cytokine Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic Publishers 1994

Authors and Affiliations

  • Ning Su
    • 1
    • 2
    • 3
  • John O. Ojeifo
    • 1
    • 2
    • 3
  • Alexander MacPherson
    • 1
    • 2
    • 3
  • James A. Zwiebel
    • 1
    • 2
    • 3
  1. 1.Departments of Medicine (Division of Hematology)Georgetown University Medical CenterWashington, DCUSA
  2. 2.PathologyGeorgetown University Medical CenterWashington, DCUSA
  3. 3.Vincent T. Lombardi Cancer CenterGeorgetown University Medical CenterWashington, DCUSA

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