Uses for monoclonal antibodies
Monoclonal antibodies are widely used as diagnostic and research reagents. Their introduction into human therapy has been much slower.
In some in vivo applications, the antibody itself is sufficient. Once bound to its target, it triggers the normal effector mechanisms of the body.
In other cases, the monoclonal antibody is coupled to another molecule, for example
a fluorescent molecule to aid in imaging the target
a strongly-radioactive atom, such as Iodine-131 to aid in killing the target.
Some monoclonal antibodies that have been introduced into human medicine
To suppress the immune system
Muromonab-CD3 (OKT3) and two humanized anti-CD3 monoclonals. Bind to the CD3 molecule on the surface of T cells. Used to prevent acute rejection of organ, e.g., kidney, transplants. The humanized versions show promise in inhibiting the autoimmune destruction of beta cells in Type 1 diabetes mellitus.
Infliximab (Remicade®). Binds to tumor necrosis factor-alpha (TNF-α). Shows promise against some inflammatory diseases such as rheumatoid arthritis (by blunting the activity of Th1 cells). Side-effects: can convert a latent case of tuberculosis into active disease; can induce the formation of autoantibodies (by promoting the development of Th2 cells).
Omalizumab (Xolair®). Binds to IgE thus preventing IgE from binding to mast cells. Shows promise against allergic asthma.
Daclizumab (Zenapax®). Binds to part of the IL-2 receptor produced at the surface of activated T cells. Used to prevent acute rejection of transplanted kidneys. Has also showed promise against T-cell lymphoma.
To kill or inhibit malignant cells
Rituximab (trade name = Rituxan®). Binds to the CD20 molecule found on most B-cells and is used to treat B-cell lymphomas.
Zevalin®. This is a monoclonal antibody against the CD20 molecule on B cells (and lymphomas) conjugated to either
the radioactive isotope indium-111 (111In) or
the radioactive isotope yttrium-90 (90Y) Both are given to the lymphoma patient, the 111In version first followed by the 90Y version (in each cases supplemented with Rituxan).
Bexxar® (tositumomab). This is a conjugate of a monoclonal antibody against CD20 and the radioactive isotope iodine-131 (131I). It, too, is designed as a treatment for lymphoma. Although both Bexxar® and Zevalin® kill normal B cells, they don't harm the B-cell precursors because these do not express CD20. So, in time, the precursors can repopulate the body with healthy B cells.
On 3 February 2005, the New England Journal of Medicine reported that 59% of patients with a B-cell lymphoma were disease-free 5 years after a single treatment with 131I-tositumomab.
Herceptin® (trastuzumab). Binds HER2, a receptor for epidermal growth factor (EGF) that is found on some tumor cells (some breast cancers, lymphomas). The only monoclonal so far that seems to be effective against solid tumors.
Erbitux® (cetuximab). Blocks HER1, another epidermal growth factor (EGF) receptor.
Mylotarg®. A conjugate of
a monoclonal antibody that binds CD33, a cell-surface molecule expressed by the cancerous cells in acute myelogenous leukemia (AML) but not found on the normal stem cells needed to repopulate the bone marrow.
calicheamicin, a complex oligosaccharide that makes double-stranded breaks in DNA.Mylotarg® is the first immunotoxin that shows promise in the fight against cancer.
LymphoCide. Binds to CD22, a molecule found on some B-cell leukemias.
Alemtuzumab (MabCampath®). Binds to CD52, a molecule found on white blood cells. Has produced complete remission of chronic lymphocytic leukemia (for 18 months and counting).
Lym-1 (Oncolym®). Binds to the HLA-DR-encoded histocompatibility antigen that can be expressed at high levels on lymphoma cells.
Angiogenesis Inhibitors
Vitaxin. Binds to a vascular integrin (alpha-v/beta-3) found on the blood vessels of tumors but not on the blood vessels supplying normal tissues. In Phase II clinical trials, Vitaxin has shown some promise in shrinking solid tumors without harmful side effects.
Bevacizumab (Avastin®). Binds to vascular endothelial growth factor (VEGF) preventing it from binding to its receptor. Approved by the US FDA in February 2004 for the treatment of colorectal cancers.
Other
Abciximab (ReoPro®). Inhibits the clumping of platelets by binding the receptors on their surface that normally are linked by fibrinogen. Helpful in preventing reclogging of the coronary arteries in patients who have undergone angioplasty.
Monoclonal antibodies are widely used as diagnostic and research reagents. Their introduction into human therapy has been much slower.
In some in vivo applications, the antibody itself is sufficient. Once bound to its target, it triggers the normal effector mechanisms of the body.
In other cases, the monoclonal antibody is coupled to another molecule, for example
a fluorescent molecule to aid in imaging the target
a strongly-radioactive atom, such as Iodine-131 to aid in killing the target.
Some monoclonal antibodies that have been introduced into human medicine
To suppress the immune system
Muromonab-CD3 (OKT3) and two humanized anti-CD3 monoclonals. Bind to the CD3 molecule on the surface of T cells. Used to prevent acute rejection of organ, e.g., kidney, transplants. The humanized versions show promise in inhibiting the autoimmune destruction of beta cells in Type 1 diabetes mellitus.
Infliximab (Remicade®). Binds to tumor necrosis factor-alpha (TNF-α). Shows promise against some inflammatory diseases such as rheumatoid arthritis (by blunting the activity of Th1 cells). Side-effects: can convert a latent case of tuberculosis into active disease; can induce the formation of autoantibodies (by promoting the development of Th2 cells).
Omalizumab (Xolair®). Binds to IgE thus preventing IgE from binding to mast cells. Shows promise against allergic asthma.
Daclizumab (Zenapax®). Binds to part of the IL-2 receptor produced at the surface of activated T cells. Used to prevent acute rejection of transplanted kidneys. Has also showed promise against T-cell lymphoma.
To kill or inhibit malignant cells
Rituximab (trade name = Rituxan®). Binds to the CD20 molecule found on most B-cells and is used to treat B-cell lymphomas.
Zevalin®. This is a monoclonal antibody against the CD20 molecule on B cells (and lymphomas) conjugated to either
the radioactive isotope indium-111 (111In) or
the radioactive isotope yttrium-90 (90Y) Both are given to the lymphoma patient, the 111In version first followed by the 90Y version (in each cases supplemented with Rituxan).
Bexxar® (tositumomab). This is a conjugate of a monoclonal antibody against CD20 and the radioactive isotope iodine-131 (131I). It, too, is designed as a treatment for lymphoma. Although both Bexxar® and Zevalin® kill normal B cells, they don't harm the B-cell precursors because these do not express CD20. So, in time, the precursors can repopulate the body with healthy B cells.
On 3 February 2005, the New England Journal of Medicine reported that 59% of patients with a B-cell lymphoma were disease-free 5 years after a single treatment with 131I-tositumomab.
Herceptin® (trastuzumab). Binds HER2, a receptor for epidermal growth factor (EGF) that is found on some tumor cells (some breast cancers, lymphomas). The only monoclonal so far that seems to be effective against solid tumors.
Erbitux® (cetuximab). Blocks HER1, another epidermal growth factor (EGF) receptor.
Mylotarg®. A conjugate of
a monoclonal antibody that binds CD33, a cell-surface molecule expressed by the cancerous cells in acute myelogenous leukemia (AML) but not found on the normal stem cells needed to repopulate the bone marrow.
calicheamicin, a complex oligosaccharide that makes double-stranded breaks in DNA.Mylotarg® is the first immunotoxin that shows promise in the fight against cancer.
LymphoCide. Binds to CD22, a molecule found on some B-cell leukemias.
Alemtuzumab (MabCampath®). Binds to CD52, a molecule found on white blood cells. Has produced complete remission of chronic lymphocytic leukemia (for 18 months and counting).
Lym-1 (Oncolym®). Binds to the HLA-DR-encoded histocompatibility antigen that can be expressed at high levels on lymphoma cells.
Angiogenesis Inhibitors
Vitaxin. Binds to a vascular integrin (alpha-v/beta-3) found on the blood vessels of tumors but not on the blood vessels supplying normal tissues. In Phase II clinical trials, Vitaxin has shown some promise in shrinking solid tumors without harmful side effects.
Bevacizumab (Avastin®). Binds to vascular endothelial growth factor (VEGF) preventing it from binding to its receptor. Approved by the US FDA in February 2004 for the treatment of colorectal cancers.
Other
Abciximab (ReoPro®). Inhibits the clumping of platelets by binding the receptors on their surface that normally are linked by fibrinogen. Helpful in preventing reclogging of the coronary arteries in patients who have undergone angioplasty.
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