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Bavituximab ?
Monoclonal antibody
Type whole antibody
Source chimeric (mouse/human)
Target phosphatidylserine
Identifiers
CAS number 648904-28-3
ATC code none
Chemical data
Formula C6446H9946N1702O2042S42 
Mol. mass 145.3 kDa
Pharmacokinetic data
Half life 30 hrs
Therapeutic considerations
Pregnancy cat.  ?
Legal status
Routes infusion

Bavituximab is a chimeric monoclonal antibody designed for the treatment of cancers and viral infections.[1]

Contents

Mechanism of action

Bavituximab binds to phosphatidylserine which is exposed on the surface of certain atypical animal cells, including tumour cells and cells infected with any of six different families of virus. These viral families contain the the viruses hepatitis C, influenza A and B, HIV 1 and 2, measles, respiratory syncytial virus and pichinde virus, which is a model for the deadly Lassa hemorrhagic fever[2]. Other cells are not affected since phosphatidylserine normally is only intracellular.[3]

Bavituximab binds to various aminophospholipids and is dependent on interaction with plasma protein beta-2 glycoprotein I to mediate binding.

These target aminophospholipids, usually residing only on the inner leaflet of the plasma membrane of cells, become exposed in virally infected, damaged or malignant cells, and more generally in most cells undergoing the process of apoptosis.

The antibody's binding to phospholipids alerts the body’s immune system to attack the tumor endothelial cells, thrombosing the tumor's vascular network and/or attacking free floating virally infected and metastatic cells while potentially minimizing side effects in healthy tissues.

Clinical trials

Phase 1B clinical trials have started to test bavituximab against HIV and hepatitis C viral infections.[4]

Phase I and II clinical trials are also in progress for various types of cancer.[5] Promising preliminary results have been reported from a Phase II trial of bavituximab used with docetaxel against advanced breast cancer.[6]

Other monoclonal antibodies targeting phospholipids

Additional analogs in the class include 3G4[7], 2aG4[8], 9d2[9] and Hu3g4[citation needed].

References

  1. ^ Statement on a nonproprietary name adopted by the USAN council
  2. ^ Nature Medicine 14, 1357 - 1362 (2008)
  3. ^ He, J.; Yin, Y.; Luster, T. A.; Watkins, L.; Thorpe, P. E. (2009). "Antiphosphatidylserine Antibody Combined with Irradiation Damages Tumor Blood Vessels and Induces Tumor Immunity in a Rat Model of Glioblastoma". Clinical Cancer Research 15 (22): 6871. doi:10.1158/1078-0432.CCR-09-1499. PMID 19887482.  edit
  4. ^ Bavituximab Repeat-Dose Trial in Patients Co-Infected With Chronic Hepatitis C Virus and Human Immunodeficiency Virus
  5. ^ http://oralcancernews.org/wp/2009/07/peregrine-completes-patient-enrollment-in-bavituximab-trial/
  6. ^ Peregrine Pharmaceuticals Presents Promising Data From Its Phase II Bavituximab Breast Cancer Trial at 2009 ASCO Annual Meeting
  7. ^ Pharma company completes humanization of 3G4 antibody
  8. ^ He, J.; Luster, T. A.; Thorpe, P. E. (2007). "Radiation-Enhanced Vascular Targeting of Human Lung Cancers in Mice with a Monoclonal Antibody That Binds Anionic Phospholipids". Clinical Cancer Research 13 (17): 5211. doi:10.1158/1078-0432.CCR-07-0793. PMID 17785577.  edit
  9. ^ Ran; Downes, A; Thorpe, PE (2002). "Increased exposure of anionic phospholipids on the surface of tumor blood vessels". Cancer research 62 (21): 6132–40. PMID 12414638.  edit

Further reading

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