See also Cancer specific antibodies .   See also Wikipedia “List of Therapeutic monoclonal antibodies”

Commercially approved antibodies:

See the Immunology Link.      web database of mAbs with clinical indications

Examples include: (Rituximab or Daclizumab or Basiliximab or Infliximab or Palivizumab or Trastuzumab or Adalimumab or Alemtuzumab or Ibritumomab or Efalizumab or Omalizumab or Tositumomab or tositumomab or Bevacizumab or Cetuximab or Natalizumab or Catumaxomab or Panitumumab or Ranibizumab or Eculizumab or Certolizumab or Canakinumab or Catumaxomab or Golimumab or Ofatumumab or Tocilizumab or Ustekinumab or Besilesomab or Denosumab or Belimumab or Brentuximab or Denosumab or Ipilimumab or Pertuzumab or Raxibacumab or Obinutuzumab or Trastuzumab)

Mechanisms of Action:

Antibodies have exquisite specificity for binding and inactivating potentially toxic or antigenic molecules. Due to their high sepcificity, antibodies are being used for diagnosis and thearapy. The term “therapeutic antibody” refers to an antibody that is used in the treatment of disease. A therapeutic antibody may have various mechanisms of action. It may bind and neutralize the normal function of a target associated with an antigen. For example, an antibody that blocks the activity of the protein needed for the survival of a cancer cell causes the cell’s death. Another therapeutic antibody may bind and activate the normal function of a target associated with an antigen. For example, an antibody can bind to a protein on a cell and trigger an apoptosis signal. Yet another antibody may bind to a target antigen expressed only on diseased tissue; conjugation of a toxic payload (effective agent), such as a chemotherapeutic or radioactive agent, to the antibody can create an agent for specific delivery of the toxic payload to the diseased tissue, reducing harm to healthy tissue (Junyan (US 13/536584).

Antibody derived cell mediated cytotoxicity (ADCC):

The primary mode of action for mAb based therapeutics for the treatment of cancer has been antibody derived cell mediated cytotoxicity (ADCC). According to this mechanism, the Fc portion interacts with FCgamma receptors on the surface of the effector immune cells (such as monocytes and macropahges), while the antibody is bound to the surface antigen of the cancer cell through its Fab region, and results in ADCC response. For example, cetuximab, which binds to the EGFR antigen on the surface of the tumor cells is known to mediate its anit tumor activity through ADCC. Another important mode of action is direct interference of specific cell signaling pathways. For example, bevacizumab binds to the soluble VEGF and thus inhibits angiogenesis, which is important for the maintenance of tumor vasculature and tumor health. (Goswami, Antibodies, 2013, 2, 452-500, 2013)

Formation of Multimeric immune complexes:

Recombinant antibodies are in use as active ingredients in a wide variety of drugs approved for clincial use. An important group of potential antibody drug targets are monomeric soluble proteins, including many monomeri cytokines and chemokines. This category of targets is highly significant in that it comprises many molecules implicated in human diseases, but antibodies directed against them have not shown the impressive efficacy seen with some targets in other classes of target molecules. In the case of multimeric soluble taregts, bivalent IgG type antibodies form immune complexes, which vary in size depending on target, epitope, target concentraiton and antibody concentration. These immune complexes are efficiently cleared by the mononuclear phagocyte typem and/or by adhesion to red cells via CR1 receptors and subsequent shedding in the spleen or live. In contrast, current antibodies directed against monomers cannot form larger immune complexes and rather than efficiently clearing these targets can merely bind them and remain in ciruclation as tiny long lived singular complexes comprising one antibody and one to two target molecules. Since the monomers can dissociate from antibody and re-assocaite, the antibody can actually dramatically increase the in vivo concentration of bioavailable pathogenic target molecules. It has long been known that for this reason, anti-cytokine antibodies can enhance and prolong the in vivo effects of cytokiens such as IL-3, IL-4 and IL-7 in mice. In contrast to soluble monomeric targets, there are well validated multimeric soluble targets against which approved antibody drugs are directed. Examples include antibodies against TNF-alpha, treated with adalimumab and infliximab and VEGF165, treated with bevacizumab. A common feature of these successful antibodies directed against soluble multimeric targets is that they have the potential to form multimeric immune complexes with the soluble multimeric trgets, thereby resulting in their clearance through the mononuclear phagocyte system. TNF-alpha, for examle, is a soluble trimeric protein, which a typical molecule including three identical copies of the TNF-alpha polypeptide and having multiple copies of the epitopes recognized by antibodies adalimumab and inflixumab, respectively. (Beckmann, US14/123,041 and US2014/0255405).