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  • 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., IMFa)

      • Immunostimulatory cytokines (e.g., IL-2)

      • Adaptive cellular immunotherapy (e.g. lymphokine activated killer cells {LAK cells}; tumor infiltrating lymphocytes{TILs})

      • Monoclonal antibodies

Current FDA Approved Immunotherapeutic Agents

Interferon (IFN)-a:

Interferon (IFN)-b

Interferon (IFN)-g

IL-2

BCG

Levamisole

  •   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

    •   Management of immunologic disease -- Example:

    •  Approaches for gene therapy and management of cancer:

      • Cytokine gene transfer for effectors such as:

        • TNFa 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

Primary Source: Barbuto, J.A.M, Akporiaye, E.T. and Hersh, E.M. Immunopharmacology, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 916-940
Haynes, B. F., Fauci, A.S. Disorders of the Immune System, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1753-1776.
Carpenter, C. B. The Major Histocompatibility Gene Complex, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1777-1782.
Cooper,M.D, and Lawton III, A. R. Primary Immune Deficiency Diseases, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1783-1791.
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