image

image
image
image
image
image
image
image

Contents

  1. Introduction
  2. Tumor Immunology
    1. Immune System and Antigen Recognition
      1. Immunity and cancer
      2. Antibodies
      3. Cytotoxic T cells
      4. helper T cells
      5. Antigen recognition
      6. Immunotherapy for cancer
    2. Tumors are Immunogenic
      1. Specific tumor antigens
      2. Immunity and tumor growth
      3. Inefficient tumor response
    3. Immunotherapeutic Strategies
      1. Immunotherapy for cancer
      2. Vaccination
      3. Increase immune system activity
      4. Disease burden and Immunotherapy
  3. Monoclonal Antibodies
    1. Development of Monoclonal Antibodies
      1. Mechanism of action
      2. Antibody therapy
      3. Obstacles to successful therapy
    2. Clinical Applications of Monoclonal Antibodies
      1. Hematologic malignancies
      2. Solid tumors
      3. Combination therapy
  4. Cytokines and Cancer Therapy
    1. Alfa-interferon
    2. Interleukin-2
    3. GM-CSF
    4. Interleukin-12
  5. Vaccine Approaches Against Cancer
    1. Peptide, autologous, and viral vector vaccines
    2. Dendritic cell vaccines
  6. Conclusion
  7. Post Test and Evaluation

The earliest record of treating a patient with cancer comes from the Edwin Smith Papyrus, dated 1600 B.C. The Papyrus documents surgical excision of a tumor – literally, taking a knife and cutting it out. Thirty-four hundred years later in 1809, surgical excision was established as the primary method of treating solid tumors, and remains so today.

Radiation therapy came into practice around 1896, just one year after Roentgen first reported the use of x-rays for diagnostic purposes in medicine. Radiation therapy continues to have a major role in the treatment of certain tumors, particularly as an adjuvant therapy of solid tumors.

Chemotherapy is an invention of the 20th century. Pancytopenia developed in soldiers exposed to nitrogen mustard gases during World War I, prompting further exploration. By the early days of World War II, clinical trials in patients with hematologic malignancies established the efficacy of chemotherapy. Its value for adjuvant treatment of solid tumors is also well documented.

William B. Coley is often credited with first recognizing the potential role of the immune system in cancer treatment. Coley, an early 20th century New York City surgeon, observed that some of his patients with sarcoma would undergo spontaneous regression of their tumor. He associated this tumor regression with antecedent bacterial infection. Coley was the first physician to attempt to harness the power of the immune system to fight cancer.1 He deliberately infected cancer patients with bacteria and actually devised a vaccine consisting of killed bacteria to prompt tumor killing. Complete tumor regression was achieved in some patients.2 Video    Download Free RealPlayer

Not until 1976, however, was it possible to more fully understand how tumor recognition and rejection was mediated at the cellular and molecular level. In 1976, T cell growth factor—known today as interleukin-2—was identified and cloned. It was then possible to study T cells in an ex vivo laboratory situation. Cytokines such as interleukin-2 are now established agents for the treatment of tumors. As we have discovered more of the cells and molecules of the immune system, we have explored their potential role in cancer therapy. Video   Slide

This comprehensive monograph details what is considered state-of-the-art in immunotherapy for cancer, and finishes with a review of the "holy grail" – tumor vaccines. We begin with Dr. Disis' thorough review of the principles of tumor immunology. Dr. Disis gives an introduction to general immunology, the foundation of cancer immunotherapy. Her section closes with a discussion of immunotherapeutic strategies.

Dr. Bishop focuses on the development of monoclonal antibodies and their therapeutic applications. He reviews the most recent data on specific monoclonal antibodies. Dr. Weber explores the role of cytokines in cancer therapy, one of the cornerstones of immunotherapy. Finally, Dr. Morse takes us to the future of cancer immunotherapy with a discussion of the complex and sometimes controversial cancer vaccines.

The history of tumor immunology is marked by cycles of intense excitement and disappointments. Our hope is always that these therapies might yield cures – the universal object of researchers, healthcare providers, and patients. More attainable, however, is the goal of developing therapies that might change the potentially fatal course of cancer to one of long-term management.1

Albert Einstein designates this activity for 4 hours in Category 1 of the AMAPRA Credit. This activity is supported by an unrestricted educational grant from EMD Pharmaceuticals.

Learning Objectives

By participating in this CME activity, you will be able to:

  • Understand the basic principles of immunology, and strategies of cancer immunotherapy
  • Understand the development and clinical applications of monoclonal antibodies
  • Identify cytokines that play important roles in cancer immunotherapy
  • Discuss the development of cancer vaccines – obstacles, areas for further exploration, and potential applications

Continue to Tumor Immunology