Induction of Immunity Against Leukemia View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

1996

AUTHORS

S. de Vos , D. B. Kohn , W. H. McBride , H. P. Koeffler

ABSTRACT

Great strides have been made in the chemotherapeutic treatment of acute lymphocytic leukemia (ALL) and moderate success has been made in treatment of acute myelogenous leukemia (AML). At this time, progress using chemotherapy has plateaued. Novel approaches to these diseases are required. Recent experiments have shown that several poorly immunogenic solid tumors can be recognized by MHC-class I restricted CD8+ cytotoxic T lymphocytes (CTL) if the tumors are engineered by genetransfer to produce one of several cytokines, including IL-2, IL-4, IL-6, IL-7, GM-CSF, TNF-α, IFN-α and -γ, or B7/BB1. The local secretion of lymphokines, critical for CTL activation, appears to bypass a deficient helper T-cell arm of the immune system. In addition, secretion of cytokines by the tumor cells stimulates the host immune system to identify and kill the untransduced parental cells upon subsequent reimplantation; and even of potential more importance, a rejection of established cancer can occur by inducing a systemic anticancer immune response by vaccination with cytokine transduced tumor cells. We studied two different murine myeloid leukemia models using WEHI3 and C1498 cell lines, transduced with a retroviral vector coding for human IL-7 (JZEN hIL/tk neo), resulting in cytokine production up to 13 ng/106 cells/24 hrs. NIH-3T3-fibroblasts, transduced with a vector coding for human IL-2 (G1Na CV hIL-2), producing up to 21 ng/106 cells/24 hrs, mixed with parental WEHI3 leukemia were used for vaccination-studies as well. Vaccination with IL-7 producing WEHI3 clones (weekly s.c. injections of 106 cells over a period of one month) resulted in a 43% survival of mice, subsequently challenged with a lethal dose of parental leukemic cells (5]104 i.v.). Vaccination with a mixture of IL-2 producing NIH-3T3-fibroblasts and parental WEHI3 cells resulted in a systemic protection of 60% of lethally challenged mice. The same experiments performed with the C1498-model showed a strong inherent immunogenicity of irradiated parental cells, as 4 out of 5 mice survived in this group. Surprisingly, all mice died in the group vaccinated with an IL-7 producing subclone. This illustrates that the process of selecting a high-cytokine producing subclone can result in clones that no longer represent the antigenic spectrum of the parental cells. Taken together, we show that induction of a specific anti-leukemia immune response may be effective treatment for AML, especially when the tumor burden is low. More... »

PAGES

265-273

References to SciGraph publications

  • 1982-12. Intratumor immunologic heterogeneity in CANCER AND METASTASIS REVIEWS
  • Book

    TITLE

    Acute Leukemias V

    ISBN

    978-3-642-78909-0
    978-3-642-78907-6

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/978-3-642-78907-6_45

    DOI

    http://dx.doi.org/10.1007/978-3-642-78907-6_45

    DIMENSIONS

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