Table 3.
Commercial development of antiviral mAbsa
| Virus | Stage of development | mAb | Isoform | Target | Development technology | Company (location) | Indication | Reference | |
|---|---|---|---|---|---|---|---|---|---|
| Acute cytopathic | RSV | Approved | Synagis (Palivizumab; MEDI-493) | IgG1 | Glycoprotein F | Humanized | MedImmune | Prophylaxis in high risk infantsb | 111 |
| RSV | Phase 3 | Numax (Motavizumab; MEDI-524) | IgG1 | Glycoprotein F | Humanized and affinity matured from palivizumab | MedImmune | Prophylaxis in high risk infants | 53 112 | |
| Rabies | Phase 1 | CR4098 | IgG1 | Glycoprotein antigenic site III | Immune Ab phage display library | Crucell (Leiden, The Netherlands) | Post-exposure prophylaxis; use in combination | 57 c | |
| CR 57 | Glycoprotein antigenic site I | EBV immortalization | |||||||
| Rabies | Preclinical (clinical trials to start in India in 2008) | 17C7 | IgG1 | Glycoprotein, either antigenic site III or minor site A | Transgenic HuMab-Mouse (Medarex) | Massachusetts Biologic Laboratories | Post-exposure prophylaxis | 10 | |
| WNVd | Phase I | hE16 (MGAWN1) | IgG1 | Envelope (E) protein, domain III | Humanized | Macrogenics (Rockville, MD, USA) | A potential therapy for diseases associated with severe West Nile Virus infection | 113 | |
| WNV | Pre-clinical | CR4374 | IgG1 | E protein, domain III | Immune human Ab phage display library | Crucell | Protected mice from infection | 114 | |
| SARS | Pre-clinical | CR3014 CR3022 | IgG1 | S1-RBD | Immune phage display Ab library | Crucell | CR3014 protected ferrets CR3022 neutralized CR3014 escape viruses; mixture of CR3014/3022 showed synergistic effect | 116 | |
| Acute cytopathic/latent reactivation | CMV | Phase 2 | TI-23 | IgG1 | Envelope glycoprotein gb | Human hybridoma | Teijin Pharma (Tokyo, Japan) | Treatment of CMV Retinitis in HIV individuals / CMV pneumonia in bone marrow transplantation—individuals | 117 |
| CMV | Information not available | HCMV37 | IgG1 | Envelope glycoprotein gb | Humanized | Scotgen Biopharmaceuticals (Aberdeen, UK; closed doors in 1997) | HCMV infections in immunocompromised individuals | 118 | |
| EBV | Phase 2 | Rituxan (Rituximab) | IgG1 | CD20 | Chimeric | Genentech (S. San Francisco, CA, USA) | Treatment, EBV-associated post-transplant lymphoproliferative disorders (interstitial pneumonia) | 119 | |
| VZV | Preclinical | TI-57 | IgG1 | Envelope glycoprotein III | Human hybridoma | Teijin Pharma | Treatment of Varicella Zoster | 120 | |
| Chronic, non-cytopathic | HIV | Phase 2 | TNX-355 | IgG4 | CD4 | Humanized | Genentech | Treatment | 121 |
| HIV | Phase 1 | KD-247 | IgG1 | gp120-V3 tip | Humanized | Kaketsuken-Chemo-Sero-Therapeutic Research Institute (Kumamoto, Japan) | Treatment | 84 | |
| HIV | Phase 1 | PRO140 | IgG4 | CCR5 | Humanized | Progenics Pharmaceuticals (Tarrytown, NY, USA) | Treatment | 84 | |
| HIV | Phase 1 Preclinical | HGS004 HGS101 | IgG4 IgG1 | CCR5 | Abgenix XenoMouse technology | Human Genome Sciences (Rockville, MD, USA) | Treatment 5.5-fold greater potency and a broader range of activity against HIV-1 viral strains than HGS004 | 84 e | |
| HIV | Preclinical | Tarvacin (Bavituximab) | IgG1 | Aminophospholipids exposed on the surface of cells | Chimeric | Peregrine Pharmaceuticals (Tustin, CA, USA) | Treatment | f | |
| HCV | Phase 1 | Tarvacin (Bavituximab) | IgG1 | Aminophospholipid, binds to phospholipids which are derived from the host cell | Chimeric | Peregrine Pharmaceuticals | Treatment of HCV and HIV co-infection | g | |
| HCV | Phase 1 | HepeX-C (XTL-6865, cocktail of mAbs AB68 and AB65) | IgG1 | Envelope protein E2 | AB68, human hybridoma; AB65, EBV immortalization | XTL Biopharmaceuticals (Rehovot, Israel) | Treatment | 122 | |
| HCV | Preclinical | HuMax-HepC | IgG1 | Envelope protein E2 | EBV immortalization | Genmab (Copenhagen) | Prophylaxis | 123 |
aInformation collected from medical literature, manufacturers' websites and press releases.
bFor prevention and treatment of RSV infection in high risk pediatric patients, the current recommendations are Palivizumab at 15 mg/kg of body weight as an intramuscular injection monthly throughout the RSV season, generally November through April in North America. In addition, the American Academy of Pediatrics (AAP) currently recommends palivizumab prophylaxis for children who present to the emergency department with bronchiolitis.
chttp://www.crucell.com/R_and_D-Clincal_Development-Rabies_Antibody_Product.
dWNV establishes persistent infection in central nervous system. Neurons are infected, and destruction of bystander nerve cells and immune-mediated damage contribute to neurologic disease. Different clinical syndromes of WNV neuroinvasive disease have been described124.
e http://www.progenics.com/pro140.cfm
f http://www.peregrineinc.com/content.php?mi=MTk=
ghttp://www.peregrineinc.com/content.php?mi=Mzg= and http://www.rxpgnews.com/article_4411.shtml