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Monoclonal Antibody-Mediated Chemotherapy
Aka: Monoclonal Antibody-Mediated Chemotherapy, Monoclonal Antibody Immunoconjugate Therapy, Pertuzamab, Perjeta, Ibritumomab tiuxetan, Zevalin, Rituximab, Rituxan, Tositumomab, Bexxar, Alemtuzumab, Campath, Gemtuzumab ozogamacin, Mylotarg, Cetuximab, Erbitux, Panitumumab, Vectibix, Bevacizumab, Avastin, Trastuzumab, Herceptin, Pertuzamab, Perjeta
- See Also
- Immune Checkpoint Inhibitor
- Targeted Cancer Therapy
- Immune Checkpoint Inhibitor
- CAR T-Cell Therapy
- Small Molecule Inhibitor-Mediated Chemotherapy
- Chemotherapy
- Monoclonal Antibody
- History
- Initially targeted to CD20 on immune cells to treat Lymphoma and Leukemia
- Lead to immunosuppressive use in Autoimmune Conditions such as Rheumatoid Arthritis
- Mechanism
- Targeted to solid tumors (e.g. Breast Cancer, Lung Cancer and Colon Cancer)
- Bind extracellular Ligands and receptor binding sites
- Monoclonal antibodies act at targeted cells via oncogene downregulation or tumor cell flagging for destruction
- Pharmacokinetics
- Large molecules (150,000 Da)
- Water-soluble
- Proteins are denatured by intestinal acids (therefore must be used intravenously)
- No hepatic metabolism (therefore no significant Drug Interactions)
- Long half-lives of days to weeks
- Adverse Effects: EGFR Inhibitors
- Adverse effects related to EGFR targeted on cancer cells, but also present in skin and GI Tract
- Dermatitis often is an indicator that the EGFR inhibitor is working
- Diarrhea occurs in 50% of patients on EGFR inhibitors
- Adverse Effects: VEGF inhibitors which inhibit Angiogenesis (e.g. Avastin)
- Adverse effects are vascular related
- Bleeding
- Thrombosis
- Hypertension
- Disadvantages
- Very expensive (typically upwards of $10,000 per course)
- Preparations: Antigen Targets
- Target: Cell Surface Markers (CD20)
- Ibritumomab tiuxetan (Zevalin): Used Non-Hodgkin's Lymphoma
- Rituximab (Rituxan): Used in Non-Hodgkin's Lymphoma and Rheumatoid Arthritis
- Tositumomab (Bexxar): Used in Non-Hodgkin's Lymphoma
- Target: Cell Surface Markers (CD52)
- Alemtuzumab (Campath): Used in CLL
- Target: Cell Surface Markers (CD33)
- Gemtuzumab ozogamacin (Mylotarg): Used in AML
- Target: Epidermal Growth Factor Receptor (EGFR, HER1)
- Cetuximab (Erbitux): Used in Colon Cancer and head and neck tumors
- Panitumumab (Vectibix): Used in Colon Cancer
- EGFR agents have been effective in metastatic Colorectal Cancer (without RAS mutation)
- Adverse effects include acne, Hypomagnesemia
- Target: Vascular Endothelial Growth Factor (VEGF)
- Bevacizumab (Avastin): Used in Colon Cancer and Non-Small Cell Lung Cancer
- Target: HER2-neu
- Trastuzumab (Herceptin): Used in Breast Cancer (where HER2-neu is overexpressed)
- Trastuzumab has been very effective in HER2 positive Breast Cancer
- Pertuzamab (Perjeta)
- Adverse effects include cardiotoxicity, Diarrhea
- Preparations: Immune Checkpoint Inhibitor
- See Immune Checkpoint Inhibitor
- Target: Cytotoxic T Lymphocyte associated-4 (CTLA-4)
- Ipilimumab (Yervoy)
- Target: Programmed Cell Death Protein 1 (PD-1)
- Pembrolizumab (Keytruda)
- Nivolumab (Opdivo)
- Target: Programmed death Ligand-1 (PDL-1)
- Atezolizumab (Tecentriq)
- Avelumab (Bavencio)
- Durvalumab (Imfinzi)
- References
- Adams (2005) Nat Biotechnol 23:1147-57 [PubMed]
- Smith (2021) Am Fam Physician 103(3): 155-63 [PubMed]