Immunotherapy has been used in the treatment of disease for over a century now. The idea or concept of using a patient’s immune system to provide targeted therapy in the treatment of disease dates back to experiments conducted by von Behring and Kitasato in 1890. Their groundbreaking research determined that immunity to infectious diseases could be transferred through a serum transfusion, thus coining the term passive serotherapy.
In 1895, the first application of passive serotherapy in the treatment of cancer was performed by Hericourt and Richet. During their experiments, they immunized dogs with human sarcoma, and transferred the serum to cancer patients in an effort to provide cancer immunity. While it’s been more than 100 years since the first cancer immunotherapy trial, the FDA only recently approved the first monoclonal antibody to be used in cancer treatment.
Fast forward to today, therapeutic monoclonal antibodies are considered to be the fastest and most promising class of new therapeutic agents used in the treatment of all manner of health conditions. While many predicted and appreciated the therapeutic potential of monoclonal antibodies over the past century, it was not until 1975 when Kohler and Milstein developed mouse hybridoma technology that the ability to produce monoclonal antibodies and direct them against a specific target antigen became a reality for doctors and patients alike.
Monoclonal antibody (mAb) therapy refers to treatment with monoclonal antibodies with the goal of suppressing immune function, destroying target cells or to treating specific inflammatory diseases like Rheumatoid Arthritis. Monoclonal antibodies with clinical implications can be divided into the following categories: murine monoclonal antibodies, humanized antibodies, chimeric antibodies and human antibodies. Monoclonal antibodies have multiple uses in health care, as noted by the table below.
It is worth noting that ⅔ of the mAb products in use today are used for transplant rejection, cancer, antiviral prophylaxis, antithrombotic treatments, autoimmune diseases and various infectious diseases. For example, Edrecolomab is used to treat solid tumors in cancer patients. Enlimomab is used to ameliorate and mitigate against organ transplant rejection. Infliximab is frequently used as therapy for Rheumatoid Arthritis and Crohn’s Disease.
Additional examples include: OKT3 is used to prevent organ transplant rejection. Palivizumab is used to treat RSV (respiratory syncytial virus). Rituximab is commonly employed in the treatment of various forms of leukemia and lymphoma. Rhumabvegf is used to treat solid tumors in many types of cancer. Transtuzumab is used to treat patients that have been diagnosed with metastatic breast cancer.
The table below provides a summary of all of the therapeutic monoclonal antibodies in use today, including details on their targeted antigens and the various health conditions they used to treat or prevent:
| Antibody Name | Target Antigen | Condition Treated or Prevented |
|---|---|---|
| Abciximab (ReoPro) | Glycoprotein IIbIIIareceptor | Complications of coronary angioplasty |
| ABX-CBL | CD147 | GVHD |
| ABX-EGF | EGFr | EGF-dependent human tumor |
| ABX-IL8 | IL-8 | Rheumatoid arthritis, psoriasis |
| AcuTect | Diagnosis of acute venous thrombosis | |
| Adalimumab (Humira) | TNF | Rheumatoid arthritis |
| AFP-Scan | AFP | Detection of liver and germ cell cancers |
| Alemtuzumab (Campath) | CD52 | B cell chronic lymphocytic leukemia, multiple sclerosis, kidney transplant rejection |
| Apolizumab (Remitogen) | 1D10 antigen | B cell non-Hodgkin’s lymphoma, solid tumors |
| Arcitumomab (CEA-Scan) technetium-99m labeled | Carcinoembryonic antigen | Presence, location and detection of recurrent and metastatic colorectal cancer |
| Anti-CD11a hu1 124 | CD11a | Psoriasis |
| Basiliximab (Simulect) | CD25 (IL-2 receptor) | Allograft rejection |
| Bectumomab | Non-Hodgkin’s lymphoma | |
| Bevacizumab (Avastin) | VEGF | Metastatic renal cell carcinoma |
| CapromahPendetide (Prostascint) indium-111 labeled | Prostate membrane specific antigen (PMSA) | Radioimmunoscintigraphy for prostate cancer |
| Cetuximab | EGFr | Head and neck, breast, pancreatic, colorectal cancers |
| CEACide | Carcinoembryonic antigen | Colorectal cancer |
| Daclizumab (Zenapax) | CD25 (IL-2 receptor) | Allograft rejection |
| Edrecolomab (Panorex) | 17-1A cell surface antigen | Colorectal cancer |
| Efalizumab (Xanelim) | CD11a | Rheumatoid arthritis |
| Enlimomab | CD54 (ICAM-1) | Organ transplant rejection |
| Epratuzumab (LymphoCide) | CD22 | Non-Hodgkin’s lymphoma |
| Gemtuzumabozogamicin Mylotarg | CD33 calicheamicin | Acute myeloid leukemia |
| Hu23F2G (LeukArrest) | CD11/18 (leukointegrin) | Ischemic stroke |
| Hu1124 | CD11a | Psoriasis |
| Ibritumomab tiuxetan (Zevalin) | CD20 | B cell non-Hodgkin’s lymphoma |
| Igovomab (Indimacis 125) | Tumor-associated antigen CA125 | Detection of ovarian adenocarcinoma |
| Imciromab pentetate (Myoscint) | Human cardiac myosin | Myocardial infarction imaging |
| IMC-C225 (ERBITUX) | EGFR | EGF-dependent human tumor |
| Infliximab (Remicade) | TNF-α | Crohn’s disease, rheumatoid arthritis |
| Inolimomab | IL-2 receptor | Organ transplant rejection |
| LDP-01 | β2 integrin | Stroke, kidney transplant rejection |
| LDP-02 | α4β7 integrin receptor | Crohn’s disease, ulcerative colitis |
| LeuTech 99cTc-Anti-CD15 anti-granulocyte antibody | CD15 | Imaging infection sites |
| Lerdelimumab | TGFb2 | Glaucoma, cataract |
| Lym-1 yttrium-90 labeled | HLA-DR | Non-Hodgkin’s lymphoma |
| LymphoScan | CD22 | Detection of B cell non-Hodgkin’s lymphoma |
| MAK-195F | TNF-α | Hyperinflammatory response in sepsis syndrome |
| MDX-33 | CD64 | Idiopathic thrombocytopenia purpura |
| MDX-H210 | Bispecific HER2 × CD64 | Breast, colorectal, kidney, ovarian, prostate cancers |
| MDX-447 | Bispecific EGFR × CD64 | Head, neck, renal cancers |
| Mitumomab (BEC2) | GD3-idiotypic | Small cell lung cancer, melanoma |
| Muromonab (Orthoclone OKT3) | CD3 | Allograft rejection |
| Natalizumab (Antegren) | α-4 integrin (VLA-4) | Multiple sclerosis, Crohn’s disease |
| Nebacumab (Centoxin) | Bacterial endotoxins | Gram-negative bacteria sepsis |
| Nofetumomab (Verluma) | Carcinoma-associated antigen | Detection of small cell lung cancer |
| OctreoScan indium-111 labeled | Somatostatin receptor | Immunoscintigraphic localization of primary and metastatic neuroendocrine tumors that contain somatostatin receptors |
| Olizuma, rhuMAb-E25 | Ig-E | Allergic asthma, allergic rhinitis |
| Oncolym (131Lym-1) iodine-131 labeled | HLA-DA | B cell non-Hodgkin’s lymphoma |
| Omalizumab (Xolair) | IgE | Allergic asthma, allergic rhinitis |
| Oregovomab (OvaRex) | Tumor-associated antigen CA125 | Ovarian cancer |
| ORTHOCLONE OKT4A | CD4 | CD4-mediated autoimmune diseases, allograft rejection |
| Palivizumab (Synagis) | Antigenic site of the F protein of respiratory syncytial virus (F gp) | Respiratory syncytial virus infection |
| Pexelizumab (5G1.1-SC) | Complement C5 | AMI, UA, CPB, PTCA |
| Priliximab | CD4 | Crohn’s disease, multiple sclerosis |
| Regavirumab | Cytomegalovirus (CMV) | Acute CMV disease |
| Rituximab (Rituxan) | CD20 | Non-Hodgkin’s lymphoma |
| Satumomab pendetide (OncoScint CR/OV) | Tumor-associated glycoprotein-72 | Detection of colorectal and ovarian cancers |
| Sevirumab (Protovir) | Cytomegalovirus (CMV) | Prevention of CMV infection in bone marrow transplant patients |
| Siplizumab (MEDI-507) | CD2 | Acute GVHD, psoriatic arthritis |
| Smart M195 | CD33 | Acute myeloid leukemia, myelodysplastic syndrome |
| Sulesomab (LeukoScan) technetium-99m labeled | Surface granulocyte nonspecific cross-reacting antigen | Detection of osteomyelitis, acute atypical appendicitis |
| Tecnemab K1 | High molecular weight melanoma-associated antigen | Diagnosis of cutaneous melanoma lesions |
| Tositumomab (Bexxar), iodine-131 attached | B cell surface protein | Non-Hodgkin’s lymphoma |
| Trastuzumab (Herceptin) | Her2/neu | Her2 positive metastatic breast cancer |
| Visilizumab (Nuvion, Smart anti-CD3) | CD3 | GVHD, ulcerative colitis |
| Vitaxin | αvβ3 integrin | Solid tumors |
| Votumumab (Humaspect) | Cytokeratin tumor-associated antigen | Detection of carcinoma of colon and rectum |
| YM-337 | GPIIb/IIIa | Prevention of platelet aggregation |
| Zolimomab | CD5, ricin A-chain toxin | GVHD |