融合卵巢癌和树突细胞刺激T细胞癌症反应
http://www.100md.com
2000年9月13日
Fused ovarian cancer and dendritic cells stimulate T-cell response against tumor
By Alka Agrawal, PhD
WESTPORT, Sep 04 (Reuters Health) - Ovarian cancer cells fused with either autologous or allogeneic dendritic cells can activate cytotoxic T cells, leading to lysis of autologous tumor cells, according to Boston, Massachusetts-based researchers.
Human ovarian cancers express several known tumor antigens and probably others that have not been identified, Dr. Jianlin Gong told Reuters Health. Since dendritic cells are very good antigen-presenting cells, fusing them with tumor cells gives them the ability to present both known and unknown tumor antigens to T cells.
Dr. Gong, of Dana-Farber Cancer Institute, and colleagues fused human ovarian cancer cells with either human autologous or allogeneic dendritic cells and found that the fused cells expressed both known ovarian cancer antigens and dendritic cell-associated co-stimulatory and adhesion molecules.
As they report in the August 1st issue of The Journal of Immunology, the fused cells effectively stimulated cytotoxic T cells to selectively lyse only autologous ovarian cancer cells. Lysis proceeded through a major histocompatibility class I-restricted mechanism, the report notes.
"The present findings demonstrating human ovarian carcinoma/dendritic cell fusions thus could have potential applicability to the field of antitumor immunotherapy as vaccines and in the identification of novel ovarian carcinoma-associated antigens," the researchers write in the journal.
Dr. Gong commented to Reuters Health that ovarian cancers are usually treated with chemotherapy, so patients have few white cells from which to generate autologous dendritic cells. Since fusion of allogeneic dendritic cells are just as effective, however, she said that it should be possible to treat patients with fusions of tissue-matched dendritic cells and tumor cells. She said that she and her colleagues are writing a protocol to treat ovarian cancer patients by this method and are awaiting approval.
In a note added in proof, the researchers cite a paper in a recent issue of Nature Medicine showing that fusions of human renal cell carcinomas and allogeneic dendritic cells are effective in treating metastatic renal cancer.
J Immunol 2000;165:1705-1711. Nat Med 2000;6:332.
-Westport Newsroom 203 319 2700, http://www.100md.com
By Alka Agrawal, PhD
WESTPORT, Sep 04 (Reuters Health) - Ovarian cancer cells fused with either autologous or allogeneic dendritic cells can activate cytotoxic T cells, leading to lysis of autologous tumor cells, according to Boston, Massachusetts-based researchers.
Human ovarian cancers express several known tumor antigens and probably others that have not been identified, Dr. Jianlin Gong told Reuters Health. Since dendritic cells are very good antigen-presenting cells, fusing them with tumor cells gives them the ability to present both known and unknown tumor antigens to T cells.
Dr. Gong, of Dana-Farber Cancer Institute, and colleagues fused human ovarian cancer cells with either human autologous or allogeneic dendritic cells and found that the fused cells expressed both known ovarian cancer antigens and dendritic cell-associated co-stimulatory and adhesion molecules.
As they report in the August 1st issue of The Journal of Immunology, the fused cells effectively stimulated cytotoxic T cells to selectively lyse only autologous ovarian cancer cells. Lysis proceeded through a major histocompatibility class I-restricted mechanism, the report notes.
"The present findings demonstrating human ovarian carcinoma/dendritic cell fusions thus could have potential applicability to the field of antitumor immunotherapy as vaccines and in the identification of novel ovarian carcinoma-associated antigens," the researchers write in the journal.
Dr. Gong commented to Reuters Health that ovarian cancers are usually treated with chemotherapy, so patients have few white cells from which to generate autologous dendritic cells. Since fusion of allogeneic dendritic cells are just as effective, however, she said that it should be possible to treat patients with fusions of tissue-matched dendritic cells and tumor cells. She said that she and her colleagues are writing a protocol to treat ovarian cancer patients by this method and are awaiting approval.
In a note added in proof, the researchers cite a paper in a recent issue of Nature Medicine showing that fusions of human renal cell carcinomas and allogeneic dendritic cells are effective in treating metastatic renal cancer.
J Immunol 2000;165:1705-1711. Nat Med 2000;6:332.
-Westport Newsroom 203 319 2700, http://www.100md.com