Bavituximab
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| Monoclonal antibody | |
|---|---|
| Type | Whole antibody |
| Source | Template:Infobox drug/mab source |
| Target | phosphatidylserine |
| Clinical data | |
| Routes of administration | infusion |
| Pharmacokinetic data | |
| Biological half-life | 30 hrs |
| Identifiers | |
| CAS Number | 648904-28-3 |
| ATC code | none |
| Chemical data | |
| Formula | C6446H9946N1702O2042S42 |
| Molar mass | 145.3 kDa[[Script error: No such module "String".]] |
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 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
A phase II trial of bavituximab used with docetaxel against advanced breast cancer has yielded median progression-free survival (PFS) data of 7.4 months, a best overall response rate of 61% (28 of 46 patients) with 11% (5 of 46) of the patients achieving a clinical complete response. (This compares favorably to a separately published study of a similar patient population receiving docetaxel alone, which showed an objective response rate of only 41% with no complete responses. Median overall survival figures are not yet available. [4]
A phase II trial of bavituximab used with paclitaxel and carboplatin chemotherapy against advanced breast cancer has yielded median progression-free survival (PFS) data of 6.9 months, a best overall response rate of 74% (34 of 46 patients) with 9% (4 of 46) of the patients achieving a clinical complete response. (This compares favorably to a separately published study of a similar patient population receiving paclitaxel and carboplatin alone, which showed a median PFS of 4.8 months, an objective response rate of 62%.) Median overall survival figures are not yet available. [5]
Another phase II study of bavituximab plus paclitaxel and carboplatin is being conducted in untreated locally advanced or metastatic non-small cell lung cancer.
Other monoclonal antibodies targeting phospholipids
Additional analogs in the class include 3G4[6], 2aG4[7], 9d2[8] and Hu3g4[citation needed].
References
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- Nature Medicine, V14, p1357.
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- ↑ Statement on a nonproprietary name adopted by the USAN council
- ↑ Nature Medicine 14, 1357 - 1362 (2008)
- ↑ 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.
- ↑ New Progression-Free Survival Data From Peregrine's Bavituximab in Phase II Refractory Breast Cancer
- ↑ Phase II Advanced Breast Cancer Data to Be Presented at ASCO Highlight Promising Tumor Response and Progression-Free Survival Data With Peregrine's Bavituximab
- ↑ Pharma company completes humanization of 3G4 antibody
- ↑ 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. More than one of
|author2=and|last2=specified (help); More than one of|author3=and|last3=specified (help) - ↑ 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.
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