Home LiteratureArticle Details
PMID: 8551233 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of experimental medicine ·Vol. 183 ·No. 1 ·1996-01-01 ·Pages 283-7

Celluzzi CM, Mayordomo JI, Storkus WJ, Lotze MT, Falo LD

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Antigen Presentation Cytotoxicity, Immunologic Dendritic Cells/immunology Female Immunization Melanoma, Experimental/therapy Mice Mice, Inbred BALB C Molecular Sequence Data Neoplasms, Experimental/therapy Peptide Fragments/therapeutic use Survival Analysis Thymoma/therapy
Chemicals
Peptide Fragments
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Celluzzi C M
Department of Dermatology, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
Mayordomo J I
Storkus W J
Lotze M T
Falo L D
References (42)
42 references, click to expand
  1. Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer.
    Cancer. 1990 Nov 1;66(9):2012-6 PMID: 2224800
  2. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.
    J Exp Med. 1992 Dec 1;176(6):1693-702 PMID: 1460426
  3. Peptide binding to empty HLA-B27 molecules of viable human cells.
    Nature. 1991 May 2;351(6321):74-7 PMID: 2027387
  4. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules.
    Nature. 1991 May 23;351(6324):290-6 PMID: 1709722
  5. Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo.
    Eur J Immunol. 1994 Mar;24(3):605-10 PMID: 8125131
  6. Evidence that granulocyte macrophage-colony-stimulating factor regulates the distribution and differentiated state of dendritic cells/Langerhans cells in human lung and lung cancers.
    J Clin Invest. 1993 Feb;91(2):566-76 PMID: 7679411
  7. Peptide-priming of cytolytic T cell immunity in vivo using beta 2-microglobulin as an adjuvant.
    J Immunol. 1993 Feb 15;150(4):1244-52 PMID: 8381832
  8. Autologous melanoma vaccine induces inflammatory responses in melanoma metastases: relevance to immunologic regression and immunotherapy.
    J Invest Dermatol. 1993 Mar;100(3):335S-341S PMID: 8440919
  9. The transporters associated with antigen presentation.
    Semin Cell Biol. 1993 Feb;4(1):53-61 PMID: 8453065
  10. Dendritic cells as antigen presenting cells in vivo.
    Int Rev Immunol. 1990;6(2-3):197-206 PMID: 2152503
  11. Dendritic cell activity against primary tumors: an overview.
    In Vivo. 1993 May-Jun;7(3):187-91 PMID: 8357960
  12. Dendritic cells: antigen presentation, accessory function and clinical relevance.
    Adv Exp Med Biol. 1993;329:1-9 PMID: 8379358
  13. Costimulation of T cells for tumor immunity.
    Immunol Today. 1993 Oct;14(10):483-6 PMID: 7506034
  14. Immunological surveillance of tumors in the context of major histocompatibility complex restriction of T cell function.
    Adv Cancer Res. 1984;42:1-65 PMID: 6395653
  15. Use of synthetic peptides of influenza nucleoprotein to define epitopes recognized by class I-restricted cytotoxic T lymphocytes.
    J Exp Med. 1987 Jun 1;165(6):1508-23 PMID: 2438367
  16. Direct activation of CD8+ cytotoxic T lymphocytes by dendritic cells.
    J Exp Med. 1987 Jul 1;166(1):182-94 PMID: 2955069
  17. Perturbation of epidermal Langerhans cells in basal cell carcinomas.
    Am J Dermatopathol. 1987 Dec;9(6):465-73 PMID: 2965525
  18. Prevention of alloantibody formation after skin grafting without prolongation of graft survival by anti-L3T4 in vivo.
    Transplantation. 1988 Jun;45(6):1118-23 PMID: 3289152
  19. Introduction of soluble protein into the class I pathway of antigen processing and presentation.
    Cell. 1988 Sep 9;54(6):777-85 PMID: 3261634
  20. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report.
    N Engl J Med. 1988 Dec 22;319(25):1676-80 PMID: 3264384
  21. Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells.
    J Immunol. 1989 Feb 1;142(3):1053-9 PMID: 2464022
  22. Primary stimulation by dendritic cells induces antiviral proliferative and cytotoxic T cell responses in vitro.
    J Exp Med. 1989 Apr 1;169(4):1255-64 PMID: 2784483
  23. An antigen-independent contact mechanism as an early step in T cell-proliferative responses to dendritic cells.
    J Exp Med. 1989 Aug 1;170(2):527-42 PMID: 2526849
  24. Assembly of MHC class I molecules analyzed in vitro.
    Cell. 1990 Jul 27;62(2):285-95 PMID: 2196996
  25. Generation of class I MHC-restricted T-T hybridomas.
    J Immunol. 1990 Aug 1;145(3):804-11 PMID: 2115542
  26. Dendritic cells pulsed with protein antigens in vitro can prime antigen-specific, MHC-restricted T cells in situ.
    J Exp Med. 1990 Aug 1;172(2):631-40 PMID: 2373994
  27. Murine epidermal Langerhans cells and splenic dendritic cells present tumor-associated antigens to primed T cells.
    Eur J Immunol. 1994 Feb;24(2):315-9 PMID: 7905414
  28. Lysis of autologous melanoma cells by tumor-infiltrating lymphocytes: association with clinical response.
    J Natl Cancer Inst. 1991 Jul 3;83(13):932-7 PMID: 2067036
  29. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha.
    J Exp Med. 1994 Apr 1;179(4):1109-18 PMID: 8145033
  30. Tumour antigens. A new look for the 1990s.
    Nature. 1994 Jun 2;369(6479):357 PMID: 8018207
  31. Proliferating dendritic cell progenitors in human blood.
    J Exp Med. 1994 Jul 1;180(1):83-93 PMID: 8006603
  32. Direct analysis of tumor-associated peptide antigens.
    Curr Opin Immunol. 1994 Oct;6(5):733-40 PMID: 7530012
  33. Dendritic cells as initiators of tumor immune responses: a possible strategy for tumor immunotherapy?
    Immunol Today. 1995 Mar;16(3):117-21 PMID: 7718082
  34. Bone marrow-generated dendritic cells pulsed with a class I-restricted peptide are potent inducers of cytotoxic T lymphocytes.
    J Exp Med. 1995 Jul 1;182(1):255-60 PMID: 7540653
  35. Targeting antigen into the phagocytic pathway in vivo induces protective tumour immunity.
    Nat Med. 1995 Jul;1(7):649-53 PMID: 7585145
  36. Bone marrow-derived dendritic cells pulsed with synthetic tumour peptides elicit protective and therapeutic antitumour immunity.
    Nat Med. 1995 Dec;1(12):1297-302 PMID: 7489412
  37. Tumor antigen presentation by murine epidermal cells.
    J Immunol. 1991 May 15;146(10):3656-61 PMID: 2026885
  38. Tumor-bearing mice exhibit a progressive increase in tumor antigen-presenting cell function and a reciprocal decrease in tumor antigen-responsive CD4+ T cell activity.
    J Immunol. 1992 Jan 15;148(2):648-55 PMID: 1345922
  39. Toward a genetic analysis of tumor rejection antigens.
    Adv Cancer Res. 1992;58:177-210 PMID: 1546558
  40. Identification of proliferating dendritic cell precursors in mouse blood.
    J Exp Med. 1992 May 1;175(5):1157-67 PMID: 1569392
  41. Serum proteases alter the antigenicity of peptides presented by class I major histocompatibility complex molecules.
    Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):8347-50 PMID: 1518868
  42. Cell biology of antigen processing and presentation to major histocompatibility complex class I molecule-restricted T lymphocytes.
    Adv Immunol. 1992;52:1-123 PMID: 1442305
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
Published
1996-01-01
Pages
283-7
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192396
Subset
IM
Grants
NIAMS NIH HHS · ARO11884 · United States
Corrections
CommentIn
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]