The use of chelated radionuclide (samarium-153- ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing Journal Article
| Authors: | Chakraborty, M.; Wansley, E. K.; Carrasquillo, J. A.; Yu, S.; Paik, C. H.; Camphausen, K.; Becker, M. D.; Goeckeler, W. F.; Schlom, J.; Hodge, J. W. |
| Article Title: | The use of chelated radionuclide (samarium-153- ethylenediaminetetramethylenephosphonate) to modulate phenotype of tumor cells and enhance T cell-mediated killing |
| Abstract: | Purpose: Exposing human tumor cells to sublethal doses of external beam radiation up-regulates expression of tumor antigen and accessory molecules, rendering tumor cells more susceptible to killing by antigen-specific CTLs. This study explored the possibility that exposure to palliative doses of a radiopharmaceutical agent could alter the phenotype of tumor cells to render them more susceptible to T cell - mediated killing. Experimental Design: Here, 10 human tumor cell lines (4 prostate, 2 breast, and 4 lung) were exposed to increasing doses of the radiopharmaceutical samarium-153- ethylenediaminetetramethylenephosphonate (153Sm-EDTMP) used in cancer patients to treat pain due to bone metastasis. Fluorescence-activated cell sorting analysis and quantitative real-time PCR analysis for expression of five surface molecules and several tumor-associated antigens involved in prostate cancer were done. LNCaP human prostate cancer cells were exposed to 153Sm-EDTMP and incubated with tumor-associated antigen-specific CTL in a CTL killing assay to determine whether exposure to 153Sm-EDTMP rendered LNCaP cells more susceptible toTcell - mediated killing. Results: Tumor cells up-regulated the surface molecules Fas (100% of cell lines up-regulated Fas), carcinoembryonic antigen (90%), mucin-1 (60%), MHC class 1 (50%), and intercellular adhesion molecule-1 (40%) in response to 153Sm-EDTMP. Quantitative real-time PCR analysis revealed additional up-regulated tumor antigens. Exposure to 153Sm-EDTMP rendered LNCaP cells more susceptible to killing by CTLs specific for prostate-specific antigen, carcinoembryonic antigen, and mucin-1. Conclusions: Doses of 153Sm-EDTMP equivalent to palliative doses delivered to bone alter the phenotype of tumor cells, suggesting that 153Sm-EDTMP may work synergistically with immunotherapy to increase the susceptibility of tumor cells to CTL killing. © 2008 American Association for Cancer Research. |
| Keywords: | controlled study; treatment outcome; human cell; bone metastasis; cancer radiotherapy; radiation dose; flow cytometry; antigen expression; prostate specific antigen; phenotype; metabolism; cancer immunotherapy; lung neoplasms; carcinoembryonic antigen; fas antigen; cancer pain; cell line, tumor; breast neoplasms; tumor antigen; prostatic neoplasms; lung tumor; gene expression regulation; gene expression regulation, neoplastic; immunology; antigen specificity; dosimetry; quantitative analysis; breast tumor; prostate tumor; breast carcinoma; cytotoxic t lymphocyte; tumor cell line; t-lymphocytes, cytotoxic; chelation therapy; tumor immunity; lung carcinoma; real time polymerase chain reaction; upregulation; mucin 1; radioisotope; radioisotopes; fluorescence activated cell sorting; cell separation; organometallic compound; organometallic compounds; intercellular adhesion molecule 1; t lymphocyte activation; cell strain lncap; prostate carcinoma; major histocompatibility antigen class 1; cell mediated cytotoxicity; organophosphorus compounds; lexidronam samarium sm 153; organophosphorus compound; samarium; samarium ethylenediaminetetramethylenephosphonate |
| Journal Title: | Clinical Cancer Research |
| Volume: | 14 |
| Issue: | 13 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 2008-07-01 |
| Start Page: | 4241 |
| End Page: | 4249 |
| Language: | English |
| DOI: | 10.1158/1078-0432.ccr-08-0335 |
| PUBMED: | 18594006 |
| PROVIDER: | scopus |
| PMCID: | PMC3407883 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: CCREF" - "Source: Scopus" |
