Hematology and Oncology Book

Tranfusion

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Monoclonal Antibody-Mediated Chemotherapy

Aka: Monoclonal Antibody-Mediated Chemotherapy, Monoclonal Antibody Immunoconjugate Therapy
  1. See Also
    1. Monoclonal Antibody
  2. History
    1. Initially targeted to CD20 on immune cells to treat Lymphoma and Leukemia
    2. Lead to immunosuppressive use in Autoimmune Conditions such as Rheumatoid Arthritis
  3. Mechanism
    1. Targeted to solid tumors (e.g. Breast Cancer, Lung Cancer and Colon Cancer)
    2. Bind extracellular Ligands and receptor binding sites
  4. Phamaracokinetics
    1. Large molecules (150,000 Da)
    2. Water-soluble
    3. Proteins are denatured by intestinal acids (therefore must be used intravenously)
    4. No hepatic metabolism (therefore no significant Drug Interactions)
    5. Long half-lives of days to weeks
  5. Adverse Effects: General
    1. Older monoclonal antibodies were produced in mice and resulted in hypersensitivity
    2. Newer drugs use a greater percentage of human antibodies (65-100%)
  6. Adverse Effects: EGFR Inhibitors
    1. Adverse effects related to EGFR targeted on cancer cells, but also present in skin and GI tract
    2. Dermatitis often is an indicator that the EGFR inhibitor is working
    3. Diarrhea occurs in 50% of patients on EGFR inhibitors
  7. Adverse Effects: VEGF inhibitors which inhibit Angiogenesis (e.g. Avastin)
    1. Adverse effects are vascular related
    2. Bleeding
    3. Thrombosis
    4. Hypertension
  8. Disadvantages
    1. Very expensive (typically upwards of $10,000 per course)
  9. Agents
    1. Target: Cell Surface Markers (CD20)
      1. Ibritumomab tiuxetan (Zevalin): Used Non-Hodgkin's Lymphoma
      2. Rituximab (Rituxan): Used in Non-Hodgkin's Lymphoma and Rheumatoid Arthritis
      3. Tositumomab (Bexxar): Used in Non-Hodgkin's Lymphoma
    2. Target: Cell Surface Markers (CD52)
      1. Alemtuzumab (Campath): Used in CLL
    3. Target: Cell Surface Markers (CD33)
      1. Gemtuzumab ozogamacin (Mylotarg): Used in AML
    4. Target: Epidermal Growth Factor Receptor (EGFR, HER1)
      1. Cetuximab (Erbitux): Used in Colon Cancer and head and neck tumors
      2. Panitumumab (Vectibix): Used in Colon Cancer
    5. Target: Vascular Endothelial Growth Factor (VEGF)
      1. Bevacizumab (Avastin): Used in Colon Cancer and Non-Small Cell Lung Cancer
    6. Target: HER2-neu
      1. Trastuzumab (Herceptin): Used in Breast Cancer (where HER2-neu is overexpressed)
  10. References
    1. Adams (2005) Nat Biotechnol 23:1147-57 [PubMed]

Monoclonal antibody immunoconjugate therapy (C0854646)

Concepts Therapeutic or Preventive Procedure (T061)
Italian Terapia con anticorpo monoclonale immuno-coniugato
Japanese 免疫抱合モノクローナル抗体療法, メンエキホウゴウモノクローナルコウタイリョウホウ
English Monoclonal antibody immunoconjugate therapy
Czech Léčba imunokonjugovanou monoklonální protilátkou
Hungarian Monoklonális antitest immunkonjugációs kezelés
French Traitement par anticorps monoclonaux conjugués
Portuguese Terapia imunoconjugada com anticorpo monoclonal
Spanish Tratamiento con anticuerpos monoclonales inmunoconjugados
Dutch monoclonale antistof immuno-geconjugeerde therapie
German Therapie mit immunkonjugierten monoklonalen Antikoerpern
Sources
Derived from the NIH UMLS (Unified Medical Language System)


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