Peptide-pulsed dendritic cells induce antigen-specific, CTL-mediated protective tumor immunity

被引:646
作者
Celluzzi, CM
Mayordomo, JI
Storkus, WJ
Lotze, MT
Falo, LD
机构
[1] UNIV PITTSBURGH,SCH MED,DEPT DERMATOL,MED CTR,PITTSBURGH,PA 15213
[2] UNIV PITTSBURGH,MED CTR,DEPT SURG MOLEC GENET & BIOCHEM,PITTSBURGH,PA 15213
[3] UNIV PITTSBURGH,MED CTR,PITTSBURGH CANC INST,PITTSBURGH,PA 15213
关键词
D O I
10.1084/jem.183.1.283
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cytotoxic T lymphocytes (CTLs) are a critical component of the immune response to tumors. Tumor-derived peptide antigens targeted by CTLs are being defined for several human tumors and are potential immunogens for the induction of specific antitumor immunity. Dendritic cells (DC) are potent antigen-presenting cells (APCs) capable of priming CTL responses in vivo. Here we show that major histocompatibility complex class I-presented peptide antigen pulsed onto dendritic APCs induces protective immunity to lethal challenge by a tumor transfected with the antigen gene. The immunity is antigen specific, requiring expression of the antigen gene by the tumor target, and is eliminated by in vivo depletion of CD8(+) T cells. Furthermore, mice that have rejected the transfected tumor are protected from subsequent challenge with the untransfected parent tumor. These results suggest that immunization strategies using antigen-pulsed DC may be useful for inducing tumor-specific immune responses.
引用
收藏
页码:283 / 287
页数:5
相关论文
共 45 条
[1]   LYSIS OF AUTOLOGOUS MELANOMA-CELLS BY TUMOR-INFILTRATING LYMPHOCYTES - ASSOCIATION WITH CLINICAL-RESPONSE [J].
AEBERSOLD, P ;
HYATT, C ;
JOHNSON, S ;
HINES, K ;
KORCAK, L ;
SANDERS, M ;
LOTZE, M ;
TOPALIAN, S ;
YANG, J ;
ROSENBERG, SA .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1991, 83 (13) :932-937
[2]   PREVENTION OF ALLOANTIBODY FORMATION AFTER SKIN-GRAFTING WITHOUT PROLONGATION OF GRAFT-SURVIVAL BY ANTI-L3T4 INVIVO [J].
AUCHINCLOSS, H ;
GHOBRIAL, RRM ;
RUSSELL, PS ;
WINN, HJ .
TRANSPLANTATION, 1988, 45 (06) :1118-1123
[3]   PERTURBATION OF EPIDERMAL LANGERHANS CELLS IN BASAL-CELL CARCINOMAS [J].
AZIZI, E ;
BUCANA, C ;
GOLDBERG, L ;
KRIPKE, ML .
AMERICAN JOURNAL OF DERMATOPATHOLOGY, 1987, 9 (06) :465-473
[4]   USE OF SYNTHETIC PEPTIDES OF INFLUENZA NUCLEOPROTEIN TO DEFINE EPITOPES RECOGNIZED BY CLASS-I-RESTRICTED CYTOTOXIC LYMPHOCYTES-T [J].
BASTIN, J ;
ROTHBARD, J ;
DAVEY, J ;
JONES, I ;
TOWNSEND, A .
JOURNAL OF EXPERIMENTAL MEDICINE, 1987, 165 (06) :1508-1523
[5]  
Becker Y, 1993, In Vivo, V7, P187
[6]   PEPTIDE BINDING TO EMPTY HLA-B27 MOLECULES OF VIABLE HUMAN-CELLS [J].
BENJAMIN, RJ ;
MADRIGAL, JA ;
PARHAM, P .
NATURE, 1991, 351 (6321) :74-77
[7]   TOWARD A GENETIC-ANALYSIS OF TUMOR REJECTION ANTIGENS [J].
BOON, T .
ADVANCES IN CANCER RESEARCH, 1992, 58 :177-210
[8]   COSTIMULATION OF T-CELLS FOR TUMOR-IMMUNITY [J].
CHEN, LP ;
LINSLEY, PS ;
HELLSTROM, KE .
IMMUNOLOGY TODAY, 1993, 14 (10) :483-486
[9]   MURINE EPIDERMAL LANGERHANS CELLS AND SPLENIC DENDRITIC CELLS PRESENT TUMOR-ASSOCIATED ANTIGENS TO PRIMED T-CELLS [J].
COHEN, PJ ;
COHEN, PA ;
ROSENBERG, SA ;
KATZ, SI ;
MULE, JJ .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1994, 24 (02) :315-319
[10]   IMMUNOLOGICAL SURVEILLANCE OF TUMORS IN THE CONTEXT OF MAJOR HISTOCOMPATIBILITY COMPLEX RESTRICTION OF T-CELL FUNCTION [J].
DOHERTY, PC ;
KNOWLES, BB ;
WETTSTEIN, PJ .
ADVANCES IN CANCER RESEARCH, 1984, 42 :1-65