Abstract
Immunotherapy of cancer could be possible in cases in which competent effector T cells can be induced. Such an approach depends on expression of tumour-specific antigens by the tumour cells and on the availability of sufficient costimulatory support for activation of cytotoxic T lymphocytes. Here, a strategy for helper T cell recruitment for induction of tumour-specific cytotoxic immune responses is presented. Allogenic MHC class II molecules were introduced into tumour cells by cell fusion. These hybrid cells, when injected into mice, induced rejection of an established tumour. The contribution of CD4-expressing helper T cells in the induction phase and of CD8-expressing T cells in the effector phase of the immune response was demonstrated. The approach described could be applicable to cases in which a suitable tumour antigen is present but not identified; it employs regulatory interactions that govern physiological immune responses and is designed to be minimally invasive.
MeSH Terms
Animals
Histocompatibility Antigens Class II/immunology
Hybrid Cells
Immunization
Mice
Mice, Inbred C57BL
Neoplasms, Experimental/immunology
T-Lymphocytes, Cytotoxic/immunology
T-Lymphocytes, Helper-Inducer/physiology
Tumor Cells, Cultured
Chemicals
Histocompatibility Antigens Class II
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Stuhler G
Max-Planck-Institut für Biologie, Abteilung Immungenetik, Tübingen, Germany.
Walden P
References (18)
18 references, click to expand
-
Toward a genetic analysis of tumor rejection antigens.
Adv Cancer Res. 1992;58:177-210
PMID: 1546558
-
Interleukin-2 in cancer treatment: disappointing or (still) promising? A review.
Cancer Immunol Immunother. 1993;36(3):141-8
PMID: 8439974
-
Establishment and characterization of BALB/c lymphoma lines with B cell properties.
J Immunol. 1979 Feb;122(2):549-54
PMID: 310843
-
Human cytotoxic T-cell lines with restricted specificity for squamous cell carcinoma of the head and neck.
Cancer Res. 1993 Mar 15;53(6):1461-8
PMID: 8443824
-
T cell recognition of human tumors: implications for molecular immunotherapy of cancer.
Clin Immunol Immunopathol. 1993 Feb;66(2):91-106
PMID: 8453790
-
Studies in antibody response of mice to tumour inoculation.
Br J Cancer. 1950 Dec;4(4):372-9
PMID: 14801344
-
Problems in the physiology of class I and class II MHC molecules, and of CD45.
Cold Spring Harb Symp Quant Biol. 1989;54 Pt 2:667-74
PMID: 2534841
-
Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells.
Science. 1994 Jan 28;263(5146):518-20
PMID: 7507262
-
Tumor eradication by adoptive transfer of cytotoxic T lymphocytes.
Adv Cancer Res. 1992;58:143-75
PMID: 1532109
-
Cytokine gene transfer in tumor cells as an approach to antitumor therapy.
Int J Clin Lab Res. 1992;21(4):278-82
PMID: 1591380
-
Immunization against tumor and minor histocompatibility antigens by eluted cellular peptides loaded on antigen processing defective cells.
Eur J Immunol. 1993 Oct;23(10):2606-13
PMID: 8405061
-
Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy.
Nature. 1986 Feb 20-26;319(6055):675-8
PMID: 3951539
-
Mechanisms of rejection induced by tumor cell-targeted gene transfer of interleukin 2, interleukin 4, interleukin 7, tumor necrosis factor, or interferon gamma.
Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2774-8
PMID: 8464888
-
Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines.
J Immunol. 1993 Oct 15;151(8):4209-20
PMID: 8409397
-
Immunological surveillance in neoplasia.
Transplant Rev. 1971;7:3-25
PMID: 5146537
-
Collaboration of helper and cytotoxic T lymphocytes.
Eur J Immunol. 1993 Sep;23(9):2279-86
PMID: 7690327
-
Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells.
Science. 1993 Jan 15;259(5093):368-70
PMID: 7678351
-
Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4.
Cell. 1992 Dec 24;71(7):1093-102
PMID: 1335364