1. Alemtuzumab (DB00087) Approved and Investigational Drug
Chemical Formula: C6468H10066N1732O2005S40
Molecular Weight:
Humanized monoclonal antibody specific to lymphocyte antigens. It is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) that is directed against the kD cell surface glycoprotein,CD52. The Campath-1H antibody is an IgG1 kappa with human variable framework and constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody (Campath-1G). Campath is produced in mammalian cell (Chinese hamster ovary) suspension culture in a medium containing neomycin.
Indication/Usage
Alemtuzumab (Campath) is a monoclonal antibody therapy used for treatment of B-cell chronic lymphocytic leukemia.
Pharmacodynamics
Campath is used to treat leukemia by exploiting antibody mediated lysis of CD52 presenting cells. The CD52 antigen is a cell surface protein found on essentially all B and T lymphocytes, a majority of monocytes, macrophages and most granulocytes. The CD52 antigen is not present on erythrocytes or hematopoetic stem cells. In leukemia there is an excess of B and T cells, so Campath permits selective reduction of lymphocyte populations.

2. Volume of Distribution
Mechanism of Action
Campath binds to the CD52 antigen present on most B and T lymphocytes. This binding leads to antibody-dependent lysis of leukemic cells.
Metabolism
Most likely removed by opsonization via the reticuloendothelial system when bound to B or T lymphocytes
Half-life
~288 hrs.
Volume of Distribution
* 0.18 L/kg
Patents
Patent no , Canada, approved: expired:
Drug Interactions
DB00072 (Trastuzumab): Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.
Sequence
Heavy Chain 1:
QVQLQESGPGLVRPSQTLSLTCTVSGFTFTDFYMNWVRQPPGRGLEWIGFIRDKAKGYTTEYNPSVKGRVTMLVDTSKNQFSLRLSSVTAADTAVYYCAREGHTAAPFDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

3. Experimental Properties
Light Chain 1:
DIQMTQSPSSLSASVGDRVTITCKASQNIDKYLNWYQQKPGKAPKLLIYNTNNLQTGVPSRFSGSGSGTDFTFTISSLQPEDIATYYCLQHISRPRTFGQGTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNR
Heavy Chain 2:
QVQLQESGPGLVRPSQTLSLTCTVSGFTFTDFYMNWVRQPPGRGLEWIGFIRDKAKGYTTEYNPSVKGRVTMLVDTSKNQFSLRLSSVTAADTAVYYCAREGHTAAPFDYWGQGSLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Light Chain 2:
Experimental Properties
Melting Point: 61°C (FAB fragment), 71°C (whole mAb)
Hydrophobicity: 0.431
Isoelectric Point: 8.76

4. General References Brands
Hale G, Bright S, Chumbley G, Hoang T, Metcalf D, Munro AJ, Waldmann H: Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. Blood Oct;62(4):
"Pubmed":
Riechmann L, Clark M, Waldmann H, Winter G: Reshaping human antibodies for therapy. Nature Mar 24;332(6162): "Pubmed":
IGMT "Link":
IGMT“ Link":
IGMT "Link":
Brands
CAMPATH – Genzyme Corporation
LEMTRADA - Genzyme Corporation

5. CAMPATH Formulation Used/Prescribed for Dosage Contraindications
Campath (alemtuzumab) is a recombinant DNA-derived humanized monoclonal antibody (Campath-1H) directed against the kD cell surface glycoprotein, CD52. Campath-1H is an IgG1 kappa antibody with human variable framework and constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody (Campath-1G). The Campath-1H antibody has an approximate molecular weight of 150 kD. Campath is produced in mammalian cell (Chinese hamster ovary). Campath is a sterile, clear, colorless, isotonic solution (pH ) for injection to be administered as intravenous infusion.
Formulation
Each single use vial of Campath contains 30 mg alemtuzumab, 8.0 mg sodium chloride, 1.44 mg dibasic sodium phosphate, 0.2 mg potassium chloride, 0.2 mg monobasic potassium phosphate, 0.1 mg polysorbate 80, and mg disodium edetate dihydrate. No preservatives are added.
Used/Prescribed for
Campath is a CD52-directed cytolytic antibody indicated as a single agent for the treatment of B-cell chronic lymphocytic leukemia (B-CLL)
Dosage
Administer as an IV infusion over 2 hours, Escalate to recommended dose of 30 mg/day three times per week for 12 weeks, Premedicate with oral antihistamine and acetaminophen prior to dosing  
Contraindications
None
Side- effects
Most common adverse reactions (≥ 10%): cytopenias, infusion reactions, cytomegalovirus (CMV) and other infections, nausea, emesis, diarrhea, and insomnia

6. Drug Interactions References
No formal drug interaction studies have been performed with Campath
References

7. Lemtrada Formulation Used/Prescribed for Dosage Contraindications
LEMTRADA (alemtuzumab) is a recombinant humanized IgG1 kappa monoclonal antibody directed against the cell surface glycoprotein, CD52. Alemtuzumab has an approximate molecular weight of 150kD. LEMTRADA is produced in mammalian cell (Chinese hamster ovary) suspension culture in a nutrient medium containing neomycin. Neomycin is not detectable in the final product. LEMTRADA is a sterile, clear and colorless to slightly yellow, solution (pH 7.2±0.2) for infusion to be administered as intravenous infusion.
Formulation
Each 1 mL of solution contains alemtuzumab 10 mg, dibasic sodium phosphate (1.15 mg), disodium edetate dihydrate ( mg), polysorbate 80 (0.1 mg), potassium chloride (0.2 mg), potassium dihydrogen phosphate (0.2 mg), sodium chloride (8 mg), and water for injection.
Used/Prescribed for
LEMTRADA is a CD52-directed cytolytic monoclonal antibody indicated for the treatment of patients with relapsing forms of multiple sclerosis (MS). Because of its safety profile, the use of LEMTRADA should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.
Dosage
Administer LEMTRADA by intravenous infusion over 4 hours for 2 treatment courses. First course: 12 mg/day on 5 consecutive days. Second course: 12 mg/day on 3 consecutive days 12 months after first treatment course. 
Contraindications
LEMTRADA is contraindicated in patients who are infected with Human Immunodeficiency Virus (HIV) because LEMTRADA causes prolonged reductions of CD4+ lymphocyte counts.

8. Side- effects Drug Interactions References
Most common adverse reactions (incidence ≥ 10% and > interferon beta-1a): rash, headache, pyrexia, nasopharyngitis, nausea, urinary tract infection, fatigue, insomnia, upper respiratory tract infection, herpes viral infection, urticaria, pruritus, thyroid gland disorders, fungal infection, arthralgia, pain in extremity, back pain, diarrhea, sinusitis, oropharyngeal pain, paresthesia, dizziness, abdominal pain, flushing, and vomiting.
Drug Interactions
No information provided.
References