Monoclonal antibodies
- manufactured by a technique called somatic cell hybridization.
This involves the fusion of myeloma cells with spleen cells from a mouse that has been immunized with the desired antigen. The resulting fused cells are termed a hybridoma and act as a 'factory' for producing monoclonal antibodies. The main limitation to this is that mouse antibodies are immunogenic leading to the formation of human anti-mouse antibodies (HAMAs). This problem is overcome by combining the variable region from the mouse body with the constant region from an human antibody.
Clinical examples of monoclonal antibodies:
- infliximab (anti-TNF-alpha): a chimeric monoclonal antibody; used in psoriasis, rheumatoid arthritis and Crohn's
- Certolizumab pegol (Certo-li-zu-mab) is a pegylated (pegol) humanized monoclonal antibody that targets TNF-alpha.
- rituximab, obinutuzumab, ocrelizumab (anti-CD20): used in non-Hodgkin's lymphoma, SLE, rheumatoid arthritis & refractory ITP, Ocrelizumab
- cetuximab (epidermal growth factor receptor antagonist): used in metastatic colorectal cancer and head and neck cancer
- Basiliximab (anti-CD25): in renal transplant, given at induction and day 4
- trastuzumab (HER2/neu receptor antagonist): used in metastatic breast cancer (cardiotoxic)
- alemtuzumab (anti-CD52 on the surface of lymphocytes): used in CLL (esp. in those who have failed fludarabine Rx), cutaneous T cell lymphoma, and T cell lymphoma; MS
- Ofatumumab: anti CD20 antibody. It is approved by the Food and Drug Administration for treatment of CLL in alemtuzumab-refractory cases. It is also used for therapy of other types of non-Hodgkin's lymphoma.
- Gemtuzumab (anti-CD33): used in acute myeloid leukemia
- abciximab (glycoprotein IIb/IIIa receptor antagonist): prevention of ischaemic events in patients undergoing percutaneous coronary interventions
- OKT3 (anti-CD3): used to prevent organ rejection
- Campath (anti-CD56): immunosuppression in bone marrow transplantation; lymphoproliferative disorders
- anti-D : prevention of Rhesus sensitization in pregnancy
- Tocilizumab, siltuximab (anti IL-6 receptor): used in Castleman disease (aka giant lymph node hyperplasia, lymphoid hamartoma, or angiofollicular lymph node hyperplasia; may be associated with HHV-8)
- PCSK9 inhibitors - Alirocumab, evolocumab; inactivate a protein in the liver called proprotein convertase subtilisin kexin 9 ; Effect is same as Statins. MOA: Inactivation of LDL-receptor degradation, increasing amount of LDL removed from bloodstream.
- Secukinumab (IL-17 antagonist) - ankylosing spondylitis and psoriasis