• Cancer Immunotherapy
  •  Current Approaches (many are experimental)
    • Active nonspecific immune stimulation (e.g.,ECG)
    • Active specific immune stimulation (e.g.,melacine melanoma vaccine)
    • Immunomodulators (e.g. levamisole)
    • Cytotoxic cytokines (e.g., IMF_a)
    • Immunostimulatory cytokines (e.g., IL-2)
    • Adaptive cellular immunotherapy (e.g. lymphokine activated killer cells {LAK cells}; tumor infiltrating lymphocytes{TILs})
    • Monoclonal antibodies

return to menu I--return to menu II

•   Gene Therapy
  • Gene transfer:
    • replace missing gene
    • replace inactivated gene (mutation)
    • introduce extra copies of a normally expressed gene
    • introduce a new gene, not normally present
  •   Purpose:
    • replace missing functions
    • increase existing functional capability
    • introduce a new function/capability

  return to menu I--return to menu II

  •   Management of immunologic disease -- Example:
    •  severe combined immunodeficiency syndrome (SCID) -- ADA deficiency
      • repair by retroviral ADA gene-transfer into patient lymphocytes

  return to menu I--return to menu II

  •  Approaches for gene therapy and management of cancer:
    • Cytokine gene transfer for effectors such as:
      • TNF_a into effector lymphocytes (e.g. lymphokine activated killer cells (LAK cells) or tumor-infiltrating cells (TILs))
    • DNA vaccines:
      • genes encoding tumor rejection antigens -- injected & expressed to induce tumor immunity
    • Gene-modified tumor cells as vaccines
      • tumors are transduced or transfected in vitro (for later vaccination) or
      • tumors are transduced or transfected in vivo (tumor becomes more immunogenic)
      • potentially useful genes -- encoding IL-1, IL-2, IL-4, IL-6, IL-7, IL-10, IL-12,; TNF-a, IFN-a, IFNg, B7.1, B7.2
    • Carrier cells (transduced with genes noted above) injected into the tumor or mixed with tumor cells for vaccination.
      • Rationale: immunostimulatory gene product is provided near the immunizing tumor cells

  return to menu I--return to menu II