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Therapeutic Cancer Vaccines

Therapeutic Cancer Vaccines. Edgar G. Engleman, MD. The Immune System. The immune system is our major defense against viruses, tumors and other “foreign invaders” It uses white blood cells and antibodies to fight invaders

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Therapeutic Cancer Vaccines

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  1. Therapeutic Cancer Vaccines Edgar G. Engleman, MD

  2. The Immune System • The immune system is our major defense against viruses, tumors and other “foreign invaders” • It uses white blood cells and antibodies to fight invaders • The immune system is extraordinarily precise and powerful, and when successfully deployed, its targets are destroyed with little or no collateral damage

  3. Tumors and the Immune System • Tumors present a unique challenge because they consist mainly of normal tissue components (“self”) and the immune system is trained to avoid attacking self • The solution is to either overcome the reluctance of the patient’s immune system to attack the tumor, or produce tumor-specific antibodies or white blood cells outside of the body and inject them into patients

  4. Immunotherapy with Monoclonal Antibodies • Antibodies recognizing constituents of tumors can be produced using recombinant DNA methods • These antibodies, when injected into patients, are safe and well tolerated and are becoming standard treatments for several types of tumors • But each antibody recognizes only a single tumor constituent, must be administered repeatedly over time, and is only partly effective

  5. Redirecting the Immune System Against Cancer Using Vaccines • Old concept: the inability of the immune system to recognize and attack tumors is inherent and irreversible • New discovery: the old concept is false. By introducing tumor constituents directly to the sentinels of the immune system (dendritic cells), potent anti-tumor immunity is generated

  6. Dendritic Cells (DC) are Present in Blood and Most Tissues Skin Langerhans cells Blood DC Heart DC Kidney DC A B C D Rat Tracheal DC Human Bronchiole DC Murine Tracheal DC E F G

  7. CD8 5 DC progenitor production in the bone marrow Induction of an immune response DC 2 Migration to peripheral tissue 1 Langerhans cells Dermal DC “danger signals” e.g. foreign matter Sampling of the environnment 3 Dendritic Cells: Center of the “Immuniverse” Lymph node Bone Marrow Stem cell CD34+ CD4 NK B Antibodies Lymphatics Migration to lymph nodes 4 Epidermis Dermis Skin

  8. Dendritic Cells (DC) as Therapeutic Vaccines • Goal:Induce anti-tumor immunity using DC pulsed with tumor components • Methods • Obtain DC from patient blood • Load DC with tumor components • Return DC to patients

  9. Preparation and Administration of DC Vaccine Leukapheresis Ag loading Tumor Ag DC Generation and Maturation Immune & Clinical Monitoring Vaccination Ag-Loaded DC

  10. Successful Therapeutic Vaccination in a Patient with Metastatic Colon Cancer

  11. Dendritic Cell Vaccination for the Treatment of Prostate Cancer From: Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, and Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with Sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 24:3089-94, 2006

  12. The Future for Immunotherapy is Bright • More monoclonal antibodies, including antibodies to prostate cancer • Drugs that target and activate dendritic cells • Drugs that target and activate other white blood cells – T cells, NK cells, B cells

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