mAbs Flashcards
Rituximab
Names: Rituxan Dev: IDEC Pharmaceuticals Marketed: Biogen Idec & Genentech Target: CD20 Format: Chimeric-IgG1 Year: 1997
Indication: For treatment of CD20-positive non-Hodgkins lymphoma, chronic lymphocytic leukemia, and rheumatoid arthritis.
PD: Rituximab binds to the CD20, which is predominantly expressed on mature B cells and on >90% of B-cell non-Hodgkin’s lympohomas. The antibody leads to selective killing of B-cells.
Mechanism: Complement mediated killing B lymphocytes.
Trastuzumab
Names: Herceptin Dev: UCLA/Genentech Target: HER2/neu receptor Type: humanized murine Year: 1998
Indication:For treatment of early stage HER2-positive breast cancer, or metastatic breast cancer that substantially overexpress HER2
PD: HER2 protein overexpression is observed in 25%-30% of primary breast cancers.Trastuzumab inhibits proliferation of human tumor cells through complement activation.
Mechanism:
Trastuzumab binds to the HER2 (or c-erbB2) proto-oncogene, an EGF receptor-like protein.
Adalimumab
Names: Humira Dev: Abbott Target: TNF-alpha Type: phage display Year: 2002
Indication: For treatment of RA, psoriatic arthritis, ankylosing spondylitis, and Crohn’s disease.
PD: Adalimumab binds to TNF-alpha and blocks its general cytokine effects, thereby reducing TNF-induced inflammation and halting tissue destruction.
Mechanism: binds to TNF-alpha and blocks its interaction with the p55 and p75 cell surface TNF receptors. Adalimumab also lyses surface TNF expressing cells in vitro in the presence of complement.
Infliximab
Name: Remicade Dev: J&J - Merc Target: TNF-alpha Type: chimeric murine Year: 1998
Indication: Crohn’s disease or ulcerative colitis, rheumatoid arthritis (in conjunction with methotrexate), ankylosing spondylitis, psoriatic arthritis, and juvenile arthritis.
PD: Infliximab binds to TNF alpha and inhibits binding of TNFa with its receptors. This reduces production of pro-inflammatory cytokines such as IL-1 and 6. This also limits leukocyte migration and expression of adhesion molecules by endothelial cells and leukocytes. Infliximab also limits the activation of neutrophil and eosinophil functional activity, reduces production of tissue degrading enzymes produced by synoviocytes and/or chondrocytes.
Bevacizumab
Name: Avastin Dev: Roche Target: VEGF Type: humanized Year: 2004
Indication:As part of combination therapy for metastatic colorectal cancer and HER2-negative metastatic breast cancer.
PD: Bevacizumab prevents or reduces the formation of blood vessels (angiogenesis) thereby preventing or reducing metatstatic disease progressing. Bevacizumab binds VEGF and prevents vascular endothelial growth and endothelial cell proliferation.
Mechanism: Bevacizumab binds VEGF and prevents the interaction of VEGF to its receptors (Flt-1 and KDR) on the surface of endothelial cells. This prevents blood vessel proliferation and tumour metastasis.
Raxibacumab
Name: ABthrax
Dev: CAT & HGS
Target: Anthrax PA
Type: Human - phage display
Indication: treatment of inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs.
Mechanism: Raxibacumab inhibits the binding of PA to its cellular receptors, preventing the intracellular entry of the anthrax lethal factor and edema factor, the enzymatic toxin components responsible for the pathogenic effects of anthrax toxin. It does not have direct antibacterial activity.
Pertuzumab
Name: Perjeta
Dev: Genentech
Target: Her2 dimerization domain
Type: Humanized (murine)
Indication: Pertuzumab is indicated for use in combination with trastuzumab and docetaxel for the treatment of patients with HER2-positive metastatic breast cancer.
Mechanism: Pertuzumab binds to the HER2 receptor and inhibits the ability of HER2 to interact with other HER family members (HER1, HER2, HER3, and HER4).
Belimumab
Name: Benlysta Dev: CAT/HGS - GSK Target:BLyS Type: Human (phage) Date: 2011
Indication: SLE
PD:Reduces population CD19+, CD20+, naive and activated B cells, plasma cells, SLE B-cells and and anti-dsDNA IgGs.
Mechanism: Belimumab binds to soluble human B lymphocyte stimulator protein (BLyS) and prevents its binding to receptors on B lymphocytes. BLyS:Receptor interaction is critical for survival of B lymphocytes. Consequently, B-cell mediated immunity and the autoimmune response is reduced.
Nivolumab
Name: Opdivo Dev: Ono Pharmaceuticals & Medarex (ac BMS) Target: PD1 Format: Human IgG4 Date: 2014
Indication: melanoma
Mechanism: PD-1 is expressed on the surface of activated T cells. PD-L1 is overexpressed in many tumors and its binding to PD-1 inactivates T-cells. Blocking of this inactivation allows T cells to attack the cancer.
Denosumab
Name: Prolia Dev: Amgen Target: RANKL Date: 2010 Type: Human
Indication: treatment of postmenopausal women with osteoporosis at high risk for fracture.
Mechanism: In many bone loss conditions, RANKL overwhelms the body’s natural defense against bone destruction. Denosumab prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors.
Blinatumomab
Name: Clincyto Dev: Micromet (acq Amgen) + Lonza Target: CD19 & CD3 Date:2014 Type: murine bi-specific tandem ScFv (BiTE)
Indication: acute lymphoblastic leukemia (ALL)
Mechanism: Blinatumomab enables a patient’s T cells to recognize malignant B cells. A molecule of blinatumomab combines two binding sites: a CD3 site for T cells and a CD19 site for the target B cells. CD3 is part of the T cell receptor. The drug works by linking these two cell types and activating the T cell to exert cytotoxic activity on the target cell. CD3 and CD19 are expressed in both pediatric and adult patients, making blinatumomab a potential therapeutic option for both pediatric and adult populations.
Pembrolizumab
Name: Keytruda Dev: Organon Biosciences (aqc Schering Plough acq Merck) Target: PD1 Date:2014 Type: humanized IgG4
Indication: melanoma
Mechanism: activation of T-cells
Ramucirumab
Name: Cyramza Dev: ImCLone (acq Eli) Target: VEGFR2 Date: 2014 Type: Human IgG1 (phage display)
Indication: gastric cancer
Mechanism: locking the binding of vascular endothelial growth factor (VEGF) to VEGFR2. VEGFR2 is known to mediate the majority of the downstream effects of VEGF in angiogenesis.
Vedolizumab
Name: Entyvio Dev: Takeda Target:a4b7 integrin Date:2014 Type: humanized IgG1
Indication: Ulcerative colitis, Crohn’s disease
Mechanism: blocks migration of memory T cells from migration into the GI tract by antagonizing a4b7/MAdCAM-1 interaction.
