Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells Journal Article
| Authors: | Nair, S. K.; Morse, M.; Boczkowski, D.; Cumming, R. I.; Vasovic, L.; Gilboa, E.; Lyerly, H. K. |
| Article Title: | Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells |
| Abstract: | Objective: To demonstrate the feasibility of inducing tumor antigen-specific immune responses in patients with metastatic cancer using total tumor RNA-loaded dendritic cells (DCs). Summary Background Data: The authors have shown that DCs transfected with mRNA encoding defined tumor antigens induce tumor antigen-specific T-cell responses in vitro and in vivo. There may be significant advantages to inducing immune responses against the entire repertoire of antigens expressed by a patient's autologous tumor. Methods: RNA was extracted from a metastatic colon cancer and used to load autologous DCs. The DCs were coincubated with autologous T cells and the cytolytic activity of the T cells was assessed by the ability to lyse the autologous tumor cells. RNA was then extracted from a metastatic lung cancer and used to load autologous DCs, followed by four injections of the DC vaccine given every 4 weeks. Tumor antigen-specific cytotoxic T lymphocyte activity was then evaluated by testing peripheral blood mononuclear cells for their ability to lyse an antigen-expressing target. Results: DCs transfected with the total RNA content of autologous tumor cells stimulated antigen-specific T-cell responses that are capable of recognizing and lysing autologous, primary tumor cells in vitro. Tumor-specific immune responses were induced in a patient with a carcinoembryonic antigen-expressing adenocarcinoma after immunization with autologous DCs transfected with total tumor RNA. Conclusions: DCs transfected with total tumor RNA may represent a method for inducing immune responses against the entire repertoire of tumor antigens of surgically resected malignancies. |
| Keywords: | adult; human tissue; aged; middle aged; human cell; case report; liver neoplasms; adenocarcinoma; antigen expression; cancer immunotherapy; melanoma; metastasis; dendritic cell; lung neoplasms; colonic neoplasms; lung cancer; tumor cells, cultured; transfection; tumor antigen; dendritic cells; immune response; genetic transfection; mononuclear cell; antigens, neoplasm; cancer vaccine; antigen specificity; messenger rna; feasibility studies; colon cancer; antigen recognition; cytotoxic t lymphocyte; t-lymphocytes, cytotoxic; cytolysis; technique; antigen presenting cell; t lymphocyte activation; rna extraction; lymphocyte function; immunotherapy, active; humans; human; male; priority journal; article; mixed cell culture |
| Journal Title: | Annals of Surgery |
| Volume: | 235 |
| Issue: | 4 |
| ISSN: | 0003-4932 |
| Publisher: | Lippincott Williams & Wilkins |
| Date Published: | 2002-04-01 |
| Start Page: | 540 |
| End Page: | 549 |
| Language: | English |
| DOI: | 10.1097/00000658-200204000-00013 |
| PUBMED: | 11923611 |
| PROVIDER: | scopus |
| PMCID: | PMC1422470 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
