Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells.
The polypeptide component of telomerase (TERT) is an attractive candidate for a broadly expressed tumor rejection antigen because telomerase is silent in normal tissues but is reactivated in more than 85% of cancers. Here we show that immunization against TERT induces immunity against tumors of unrelated origin. Immunization of mice with TERT RNA-transfected dendritic cells (DC) stimulated cytotoxic T lymphocytes (CTL), which lysed melanoma and thymoma tumor cells and inhibited the growth of three unrelated tumors in mice of distinct genetic backgrounds. TERT RNA-transfected human DC stimulated TERT-specific CTL in vitro that lysed human tumor cells, including Epstein Barr virus (EBV)-transformed B cells as well as autologous tumor targets from patients with renal and prostate cancer. Tumor RNA-transfected DC were used as surrogate targets in the CTL assays, obviating the difficulties in obtaining tumor cells from cancer patients. In one instance, where a tumor cell line was successfully established in culture from a patient with renal cancer, the patient's tumor cells were efficiently lysed by the CTL. Immunization with tumor RNA was generally more effective than immunization with TERT RNA, suggesting that an optimal immunization protocol may have to include TERT as well as additional tumor antigens.
Nair
S K
SK
Department of Surgery, Center for Genetic and Cellular Therapies, Duke University Medical Center, Durham, NC 27710, USA.
Heiser
A
A
Boczkowski
D
D
Majumdar
A
A
Naoe
M
M
Lebkowski
J S
JS
Vieweg
J
J
Gilboa
E
E
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D001402:B-Lymphocytes; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002472:Cell Transformation, Viral; D003713:Dendritic Cells / Q000276:immunology*; D006183:H-2 Antigens; D004854:Herpesvirus 4, Human; D006801:Humans; D007167:Immunotherapy; D007680:Kidney Neoplasms / Q000276:immunology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000276:immunology; D012313:RNA / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D013602:T-Lymphocytes, Cytotoxic; D019098:Telomerase / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014614:Vaccines, Synthetic / Q000627:therapeutic use
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D006183:H-2 Antigens; D014614:Vaccines, Synthetic; D012313:RNA; D019098:Telomerase