Monoclonal antibodies have been around since 1975. They are an effective resistance against tumors either used alone or with other therapeutic drugs.
Obstacles in Clinical use
1. Size of molecule
2. Affinity to tumor cells
3. Charge on the ion
4. Species of origin and Immunogenicity
5. Tumor associted and tumor specific antigens
6. Tumor Physiology
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Mechanism of Action
1. Complement Activation
2. Cytotoxic effector cell generation
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Trastuzumab
HER-2/neu (cerb B-2) member of Epidermal growth FActor receptor (EGFR) family overexpressed in many GI cancers and breast cancer.
Trastuzumab is a human monocloncal antibody that recognises an epitope on HER-2/neu. Mostly used in breast cancer but good results in GI cancer as well
Side Effects
Cardiomyopathy
Pulmonary
Pneumonia
Diarrhea
Bevacizumab
Vascular Endothelium Growth Factor is produced by tumor cells to aid in anguiogenesis. Bevacizumab targets these VEGF receptors
Humanised monoclonal antibody blocks binding of VEGF to its receptors
Used in metastatic colon cancer with Irinotecan, 5FU and Leucovorin Bevacizumab had a median survival of 20 mths vs 15 months and response rate of 44.8% vs 34.8%)
Hypertension is side effect but easily controlled
Other side effects also include Gastrointestinal perforations, bleeding and thrombosis
Cetuximab and Panitumumab
Against Epidermal Growth factor Receptors
These antibodies bind to the EGF receptor and block the ligand
Cetuximab is chimeric molecule where as Panitumumab is humanised
Side effects
Rash, Hypersensitivy, Malaise , diarrhoea
Ipilimumab
Cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4)
Other Uses
1. Radioimmunotherapy- Radio isotope + Monoclonal Antibody like : ibritumomab tiuxetan and tositumomab.
2. Drug Conjugates - Coupling of drugs to tumor-binding monoclonal antibodies can direct the cytotoxic drug to the tumor. An example is an anti-CD33 monoclonal antibody that is linked to calicheamicin,
3. Immunotoxins-