Monoclonal Antibody-Mediated Chemotherapy

Aka: Monoclonal Antibody-Mediated Chemotherapy, Monoclonal Antibody Immunoconjugate Therapy, Immune Checkpoint Inhibitor

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. Pharmacokinetics
   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: Immune Checkpoint Inhibitors
   1. Precautions
      1. Toxicity may be severe or even life threatening
      2. Reactions may be delayed for even a year after medication is discontinued
   2. Hypersensitivity
      1. Older monoclonal antibodies were produced in mice and resulted in hypersensitivity
      2. Newer drugs use a greater percentage of human antibodies (65-100%)
      3. Corticosteroids tapered over a 4-6 week course may be needed
   3. Diarrhea or colitis
      1. Exclude Clostridium difficile
      2. Treat symptomatically
   4. Autoimmune endocrine disorders
      1. Thyroid disease
      2. Type I Diabetes Mellitus
   5. Other inflammatory conditions
      1. Rashes
      2. Pneumonitis
      3. Hepatitis
   6. References
      1. (2018) Presc Lett 25(10): 57
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. Preparations: General Monoclonal Antibodies
   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. Preparations: Immune Checkpoint Inhibitors
    1. Target: Cytotoxic T Lymphocyte associated-4 (CTLA-4)
       1. Ipilimumab (Yervoy)
    2. Target: Programmed Cell Death Protein 1 (PD-1)
       1. Pembrolizumab (Keytruda)
       2. Nivolumab (Opdivo)
    3. Target: Programmed death Ligand-1 (PDL-1)
       1. Atezolizumab (Tecentriq)
       2. Avelumab (Bavencio)
       3. Durvalumab (Imfinzi)
    4. References
       1. Dine (2017) Asia Pac J Oncol Nurs 4(2): 127–135 [PubMed]
       2. American Cancer Society
          1. https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/immune-checkpoint-inhibitors.html
11. References
    1. Adams (2005) Nat Biotechnol 23:1147-57 [PubMed]