Panitumumab is a fully human IgG2 kappa light chain monoclonal antibody. It is approved for the treatment of EGFR-expressing metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Panitumumab binds to EGFR (similar to cetuximab), inhibiting epidermal growth factor from binding to its receptor, and prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases. It inhibits cell growth, induces apoptosis, decreases vascular growth factor production, and suppresses internalization of the EGFR. Although dermatologic and infusion-related toxicities are common following infusion of panitumumab, the distinct advantage over cetuximab is that it is fully human (ie, does not elicit HAMAs) and thus has an extended half-life in circulation. This is the first FDA-approved monoclonal antibody produced from transgenic mice expressing the human immunoglobulin gene loci.
Pertuzumab is a recombinant humanized IgG1 monoclonal antibody. It is approved for the treatment of metastatic or locally advanced HER-2/neu-positive breast cancer in combination with trastuzumab (see below) and docetaxel as neoadjuvant therapy. This antibody suppresses tumor growth by preventing heterodimerization of the human epidermal growth factor receptor HER-2/neu with other HER family members, thus inhibiting ligand-mediated intracellular signaling through MAP kinase and PI3 kinase pathways. Pertuzumab also mediates antibody-dependent cell-mediated cytotoxicity on HER-2/neu-positive tumor cells.
Ofatumumab is a human IgG1 monoclonal antibody directed against an epitope on CD20 on lymphocytes. Rituximab, the first approved CD20 monoclonal antibody (see below), also binds CD20, but to a different epitope. Ofatumumab is approved for patients with CLL who are refractory to fludarabine and alemtuzumab. Ofatumumab binds to all B cells including B-CLL. It is thought to lyse B-CLL cells in the presence of complement and to mediate antibody-dependent cellular cytotoxicity. There is a slight risk of hepatitis B virus reactivation in patients taking ofatumumab.
Ramucirumab is a human Mab that binds to VEGF receptor 2 on tumor cells as a receptor antagonist, blocking the binding of VEGF to VEGFR2. It is FDA approved for the following indications: metastatic colon cancer in combination with a FOLFIRI chemotherapy regimen (folinic acid, fluorouracil, and irinotecan), platinum-resistant metastatic small cell lung cancer in combination with docetaxel, and advanced gastric or gastroesophageal junction adenocarcinoma with or without paclitaxel.