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      1. Author :
        Beck, Benjamin H; Kim, Hyung-Gyoon; Kim, Hyunki; Samuel, Sharon; Liu, Zhiyong; Shrestha, Robin; Haines, Hilary; Zinn, Kurt; Lopez, Richard D
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2010
      5. Publication :
        Breast cancer research and treatment
      6. Products :
      7. Volume :
        122
      8. Issue :
        1
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        4T1-luc2; Adenocarcinoma; Animals; Bioware; Breast Neoplasms; Cell Line, Tumor; Chemotaxis, Leukocyte; Cytotoxicity, Immunologic; Female; Humans; Immunotherapy, Adoptive; Indium Radioisotopes; Mammary Neoplasms, Experimental; Mice; Mice, Inbred BALB C; Mice, Knockout; Neoplasm Transplantation; Radiopharmaceuticals; Receptors, Antigen, T-Cell, gamma-delta; Spleen; Tissue Distribution; T-Lymphocyte Subsets; Tomography, Emission-Computed, Single-Photon; Transplantation, Heterologous; Transplantation, Isogeneic
      12. Abstract :
        In contrast to antigen-specific alphabeta-T cells (adaptive immune system), gammadelta-T cells can recognize and lyse malignantly transformed cells almost immediately upon encounter in a manner that does not require the recognition of tumor-specific antigens (innate immune system). Given the well-documented capacity of gammadelta-T cells to innately kill a variety of malignant cells, efforts are now actively underway to exploit the antitumor properties of gammadelta-T cells for clinical purposes. Here, we present for the first time preclinical in vivo mouse models of gammadelta-T cell-based immunotherapy directed against breast cancer. These studies were explicitly designed to approximate clinical situations in which adoptively transferred gammadelta-T cells would be employed therapeutically against breast cancer. Using radioisotope-labeled gammadelta-T cells, we first show that adoptively transferred gammadelta-T cells localize to breast tumors in a mouse model (4T1 mammary adenocarcinoma) of human breast cancer. Moreover, by using an antibody directed against the gammadelta-T cell receptor (TCR), we determined that localization of adoptively transferred gammadelta-T cells to tumor is a TCR-dependant process. Additionally, biodistribution studies revealed that adoptively transferred gammadelta-T cells traffic differently in tumor-bearing mice compared to healthy mice with fewer gammadelta-T cells localizing into the spleens of tumor-bearing mice. Finally, in both syngeneic (4T1) and xenogeneic (2Lmp) models of breast cancer, we demonstrate that adoptively transferred gammadelta-T cells are both effective against breast cancer and are otherwise well-tolerated by treated animals. These findings provide a strong preclinical rationale for using ex vivo expanded adoptively transferred gammadelta-T cells as a form of cell-based immunotherapy for the treatment of breast cancer. Additionally, these studies establish that clinically applicable methods for radiolabeling gammadelta-T cells allows for the tracking of adoptively transferred gammadelta-T cells in tumor-bearing hosts.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19763820
      14. Call Number :
        PKI @ catherine.lautenschlager @
      15. Serial :
        8939
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