Monoclonal Antibodies Flashcards
Muromonab-CD3 side effects
mild flu-like symptoms, anaphylactic reactions, CNS toxicities, side effects due to suppression of the immune system (increased risk of infection and cancer)
Ustekinumab (Stelara) therapeutic uses
Psoriasis
Certolizumab (Cimzia)
pegylated humanized Fab’ fragment of a TNF-α monoclonal antibody (NO Fc region)
Golimumab (Simponi) side effects
Serious and sometimes fatal infections
Brentuximab vedotin (Adcatris) therapeutic uses
classical Hodgkin lymphoma and systemic anaplastic large cell lymphoma
Trastuzumab emtansine (Kadcyla) side effects
nausea, fatigue, headache, constipation, musculoskeletal pain, increased liver enzymes, and thrombocytopenia
What test should be performed BEFORE administering Vedolizumab(Entyvio)
Pre-existing infection including tuberculosis
Abciximab (Centorex, Reopro) MOA
Antithrombotic—helps to prevent blood clots—the Fab fragment binds to glycoprotein receptor of human platelets and inhibits aggregation
Directed against GP IIb/IIIa receptors which are integrin family of adhesion molecules
Steric hindrance of the receptor itself as opposed to direct binding to RGD binding site of the receptor
Inhibits monocyte adhesion
Inhibits vitronectin receptors (present in serum) which mediate blood coagulation as well as endothelial and smooth muscle cell proliferation
Ipilimumab (Yervoy)
Human antibody
Muromonab-CD3 therapeutic uses
Prevent acute rejection
Used to deplete T cells from donor bone marrow prior to bone marrow transplantation
Alirocumab (Praluent) side effects
injection site bruising, flu like symptoms, nose and throat irritation, GI symptoms, muscle pain, and urinary tract infection
Brentuximab vedotin (Adcatris) side effects
Chemotherapy-induced peripheral neuropathy is one of the adverse effects of the drug.
Other side effects include, nausea, vomiting, diarrhea, cough, anemia, fatigue, upper respiratory tract infection, fever, rash, thrombocytopenia, and neutropenia.
Ustekinumab (Stelara)
Human IgG1alpha monoclonal antibody
Ofatumumab (Arzerra)
Human monoclonal antibody
Abciximab (Centorex, Reopro) side effects
nausea, vomiting, dizziness, and irritation at the injection site, occasional breathing trouble, rapid or abnormal heart beat, chest pain, swelling of feet or ankles
Nivolumab (Opdivo)
Human monoclonal antibody (IgG4)
Ibritumomab (Zevalin)
Murine monoclonal antibody
Abciximab (Centorex, Reopro) therapeutic uses
emergency care in patients with heart disease caused by poor blood flow in the arteries of heart (Ischaemic cardiac complications)
Reslizumab (Cinqair) administration
Once every 4 weeks (IV infusion can take up tp 50mins)
Natalizumab (Tysabri) MOA
specific for α-4 integrin
interferes with the cellular traffic through the cellular lining of blood-brain barrier and intestines, and as a consequences produces its anti-inflammatory effects
Daclizumab (Zinbryta) therapeutic uses
Kidney transplantation
Panitumumab (Vectibix) MOA
binds to epidermal growth factor receptors (EGFR aka:HER-1) resulting in the inhibition of signal transduction pathways
Muromonab-CD3 MOA
Binds to the CD3, antigen is blocked and cannot bind to the antigen-recognition complex
Antibody binds to T lymphocytes—total circulating T cells are depleted from the blood and when the T cells reappear, the CD3 and antigen recognition complex are absent
Ibritumomab (Zevalin) therapeutic uses and how is it administered
treatment of relapsed or refractory low grade, follicular, or transformed B cell non-Hodgkin’s lymphoma and in patients with rituximab refractory follicular non-Hodgkin’s lymphoma
Administered in two steps:
- patient initially receives a single infusion of rituximab which is administered to get rid of the majority of B cells (CD20 receptors) and to limit toxicity from radiation
- The immunoconjugate linked to Indium 111 is then transfused
- 7-9 days after the infusion a second infusion of rituximab is given followed by the administration of the immunoconjugate linked to Yttrium 90
Tocilizumab(Actemra) MOA
Inhibit IL-6 receptors
—binds to soluble as well as membrane bound interleukin-6 receptors
Nivolumab (Opdivo) therapeutic uses
unseceptible or metastatic melanoma, which no longer responds to other treatments
advanced squamous cell carcinoma of head and neck and squamous non-small cell lung cancer (not a cure—just prolongs life)
Late stage liver, renal, bladder and colorectal cancer it is used to prolong life
The inhibition of PD-1 system produces natural anti-cancer response
Benefits of antibodies that target CD20 receptors
Mature B cells go through some final changes to become plasma cells which are the cells that secrete antibodies—Stem cells and Plasma cells do NOT express CD20
When you use a drug that targets CD20 it has a lot of benefits because you are not destroying stem cells and therefore do not require bone marrow transplant and you are not destroying plasma cells so the body will continue to make some antibodies and the patient will not be completely Immunocompromised
Belimumab (Benlysta) therapeutic uses
Systemic lupus erythematosus
Palvizumab (Synagis) therapeutic uses
Directed against RSV
prevention of serious lower respiratory infection caused by respiratory syncytial virus (RSV)
Rituximab (Rituxan) MOA
IgG1 specific antibody for CD20 receptor contains human constant region and murine heavy and light chains variable regions
Fab domain of the antibody binds to CD20 marker on B cells
Fc domain recruits immune effector cells and mediators for B cell lysis—lysis can be achieved by antibody-dependent cell mediated cytotoxicity and apoptosis
Infliximab (Remicade)
Chimeric antibody
Centuximab (Erbitux) therapeutic uses
treatment of head, neck and colorectal cancers and in combination with radiation therapy it is indicated for the treatment of squamous cell carcinoma (locally or regionally advanced).
However, it is not given in combination with radiation to patients who did not exhibit a good response to platinum-based therapy (cannot give with KRAS then this will not work)
For metastatic colorectal carcinoma expressing EGFR it is administered in combination with irinotecan, provided that the patients are refractory to irinotecan-based chemotherapy
Ixekizumab (Taltz)
Humanized monoclonal antibody
Tocilizumab(Actemra) side effects
upper respiratory infection, common cold, HA, and high BP
Brentuximab vedotin (Adcatris) MOA
After binding to the cell surface of the target cell, it is internalized by endocytosis and selectively targets the tumor cells
Bevacizumab (Avastin) side effects
GI perforation, hemorrhage, hypertension*, complications with wound healing, nephritic syndrome, congestive heart failure and thromboembolic events
Daclizumab (Zinbryta) MOA
binds to alpha subunit of IL-2 receptors—prevents the binding of IL-2 to its receptors
Since alpha chain is not expressed on resting T cells, entire immune response may not be suppressed
Trastuzumab emtansine (Kadcyla) MOA
Mertansine enters tumor cells, binds to tubulin and kills them and as a result, it kills the cell
Trastuzumab emtansine (Kadcyla)
Conjugated antibody made up of Trastuzumab linked to cytotoxic agent Mertansine
Certolizumab (Cimzia) MOA
neutralizes membrane-bound and soluble human TNFα in a dose-dependent manner.
Most potent antibody against TNF alpha b/c it is only a fragment and can reach the tissue
It has a high affinity for TNF-α but does NOT induce antibody-dependent cellular cytotoxicity, complement activation, or apoptosis in T cells or macrophages.
Ixekizumab (Taltz) therapeutic uses
Moderate to severe psoriasis in adults
Trastuzumab (Herceptin)
Humanized monoclonal antibody (CDR grafted IgG1)
Infliximab (Remicade) MOA
Inhibits TNF alpha
Neutralizes the effects of TNF alpha which includes its effects on IL-1 and IL-6
Reduces infiltration of inflammatory cells into the inflamed areas of joints
Suppresses the expression of adhesion molecules.
Decreases IL-6 levels.
Inhibits acute phase response.
Centuximab (Erbitux) MOA
specific for epidermal growth factor receptors (HER1) which are expressed on epithelial tissue as well as on the tumors of the colon, rectum, head and neck
Causes inhibition of EGF-mediated signal transduction events including the phosphorylation and activation of various kinases associate with EGFR
The inhibition of binding of EGF to its receptors suppresses cell growth and decreases in the production of matrix metalloproteinase and vascular endothelial growth factor (VEGF)
Tocilizumab(Actemra)
Humanized antibody
umab
Human antibody
Panitumumab (Vectibix) therapeutic uses
colorectal cancer in patients who have not responded well to standard chemotherapy
Mutations called KRAS and NRAS and BRAF
—If there is a mutation in KRAS or NRAS then this antibody will not work (must test the mutations before giving the drug)
Reslizumab (Cinqair)
Humanized monoclonal antibody
Ibritumomab (Zevalin) side effects
anemia, thrombocytopenia, neutropenia, increased risk of infection (monitor for infection for at least one year), allergic reactions including the bronchospasm and angioedema and GI discomfort
There is also some risk of secondary malignancy
Brentuximab vedotin (Adcatris)
composed of a chimeric monoclonal antibody brentuximab, which is specific for CD30 molecules and is attached to an antimitotic agent monomethyl auristatin E
Trastuzumab (Herceptin) administered with what other drugs
lapatinib or paclitaxel
Ipilimumab (Yervoy) MOA
binds to CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) which is expressed on the surface of helper T cells and transmits inhibitory signals to T cells. It is also found on regulatory T cells
CTLA-4 binds to CD80 and CD86 (B7) on antigen presenting cells
CTLA-4 regulates T cell responses in fighting disease
The antibody blocks the function of CTLA-4, resulting in a sustained immune response that attacks the cancer cells (Immune response will continue without stoping)
Muromonab-CD3
100% mouse antibody
Nivolumab (Opdivo) side effects
fatigue, shortness of breath, lack of appetite, GI symptoms, and musculoskeletal pain
Natalizumab (Tysabri)
Humanized monoclonal antibody
Bevacizumab (Avastin) MOA
directed against vascular endothelial growth factor (VEGF) receptors present on endothelial cells
VEFG promotes the proliferation of endothelial cells and formation of new blood vessels—inhibit formation of new blood vessels which will inhibit angiogenesis and the tumor dies
Panitumumab (Vectibix)
Fully human monoclonal antibody (IgG2)
Daclizumab (Zinbryta)
Humanized antibody
omab
100% murine antibody
Trastuzumab emtansine (Kadcyla) therapeutic uses
Specific for patients who are afflicted with HER2-positive metastatic breast cancer, and have been previously treated with Herceptin (NOT first line therapy)
patients who have already been treated for metastatic breast cancer or have re-developed tumor within six months of therapy
Basiliximab (Simulect)
Chimeric monoclonal antibody
Natalizumab (Tysabri) side effects
progressive multifocal leukoencephalopathy (PML), which is an opportunistic infection caused by John Cunningham (JC) virus
Tocilizumab(Actemra) therapeutic uses
administered subcutaneously for moderate to severe rheumatoid arthritis and systemic juvenile idiopathic arthritis.
could be administered with or without methotrexate
Ofatumumab (Arzerra) side effects
flu-like symptoms, upper respiratory infection, lower respiratory infection, rash, neutropenia and anemia
Centuximab (Erbitux)
Chimeric monoclonal antibody (IgG1)
Ixekizumab (Taltz) MOA
Inhibits IL-17A and IL-17A/F
IL-17 stimulates proliferation and activation of keratinocytes
Ofatumumab (Arzerra) therapeutic uses
chronic lymphocytic leukemia which is refractory to fludarabine and Alemtuzumab
Rituximab (Rituxan)
Chimeric monoclonal antibody
Golimumab (Simponi) MOA
Inhibits tumor necrosis factor α, and used as an immunosuppressive drug
Ixekizumab (Taltz) CI with what infection
Tuberculosis
Bevacizumab (Avastin)
Humanized monoclonal antibody (IgG1)
Trastuzumab (Herceptin) therapeutic uses
aggressive metastatic breasts cancer who over express HER-2
Reslizumab (Cinqair) side effects
anaphylactic reaction, chest tightness, wheezing, light- headedness, itches, and rash
Trastuzumab (Herceptin) side effects
development of ventricular dysfunction and congestive heart failure—left ventricular function must be evaluated in all patients before and during trastuzumab therapy
Patients treated with trastuzumab exhibit symptoms of cardiac dysfunction, dyspnea, peripheral edema and reduced ejection fraction.
In combination with anthracyclin and cyclophosphamide it exhibits severe cardiomyopathy.
It may cause allergic reactions, anaphylaxis and pulmonary events. Chills and fever have also been reported after first infusion.
Golimumab (Simponi) therapeutic uses
administered once a month subcutaneously for the treatment of moderate to severe rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and ulcerative colitis(in adults)
Vedolizumab(Entyvio) administration
Zero, two, and six weeks and then every 8 weeks
Alemtuzumab (Lematrada) MOA
binds CD52 receptor which is present on the surface of normal and malignant T cells—It mediates its effects via antibody-dependent lysis of target cells (T cells) after binding to CD52 receptors (also neutralizes T cells)
CD52 is not present on erythrocytes (RBC)
Golimumab (Simponi)
Human monoclonal antibody
Ibritumomab (Zevalin) MOA
IgG1 conjugated to a linker—one of the two radiation sources Indium-111 or Yttrium-90
The antibody is directed against CD20 receptor which is not shed from the cell surface and is not internalized after binding to the antibody
The antibody is supplied in two vials one containing antibody conjugated to Indium-111 and the other to Yttrium-90.
After binding to cells expressing CD20 receptors the antibody delivers radiation which enhances its killing effect and induces apoptosis and the radiation causes further damage to the cells by the formation of the free radicals
The B cells recover in about 9 months since CD20 receptor is not expressed on B cell precursors
Alemtuzumab (Lematrada)
Humanized antibody (CDR grafted IgG1)
Vedolizumab(Entyvio) therapeutic uses
ulcerative colitis and inflammatory disease
Used in patients who do not respond well to anti-TNFα therapies
Certolizumab (Cimzia) therapeutic uses
RA and Chron’s
Vedolizumab(Entyvio) MOA
Inhibits integrin α4β7 (LPAM-1, lymphocyte Peyer’s patch adhesion molecule 1)
Inhibiting the function of integrin α4β7 activity causes anti-inflammatory effect
Natalizumab (Tysabri) therapeutic uses
Multiple sclerosis and Chron’s
lesions in multiple sclerosis are caused by T lymphocytes passing through the blood-brain barrier through their interaction with the adhesion molecules on endothelial cells (high endothelial venules)
By inhibiting the adhesion molecules, we block the migration of cytotoxic and inflammatory cells into the brain or the bowel/GI tract
Certolizumab (Cimzia) side effects
decrease body’s ability to fight infection and increase the risk of serious or life-threatening infections, including severe bacterial, fungal, and/or viral infections.
GI discomfort, intestinal obstruction, diarrhea, upper respiratory infection, urinary tract infection, and arthralgia
Adalimumab (Humira) MOA
binds to TNF alpha and blocks its interaction with p55 and p75 cell surface TNF alpha receptors
Modulates biological responses that are induced or regulated by TNF alpha including the changes in the levels of the adhesion molecules
Rapidly decreases acute phase proteins, serum cytokines, and metalloproteinase
Adalimumab (Humira) cannot be given with what other drugs
TNF alpha inhibitors
ximab
Chimeric antibody
Infliximab (Remicade) therapeutic uses
treat rheumatoid arthritis and Crohn’s Disease and it may alter other immune cells
Belimumab (Benlysta) MOA
inhibits B cell activating factor. B-cell (BAFF) also referred to as B-lymphocyte stimulator, is responsible for the development and survival of B cells (inhibit production of antibodies)
Ofatumumab (Arzerra) MOA
specific for CD20 protein—its epitope is distinct from rituximab
Inhibits early stage B cell activation and cytotoxic to cells expressing CD20 (ADCC)
Basiliximab (Simulect) MOA
binds to IL-2 receptor alpha chain (CD-25 antigen) on the surface of activated T lymphocytes (IL-2 receptor alpha chain are the high affinity receptors)
inhibits IL-2 mediated activation of T cells
While in circulation it impairs the response of the immune system to the antigenic challenge
Adalimumab (Humaria) therapeutic use
Treat RA and Chron’s disease
Palvizumab (Synagis)
CDR grafted antibody
Rituximab (Rituxan) side effects
Most side effects are felt after the first treatment—immediate side effects include fever, chills and respiratory symptoms; other infusion reactions include nausea, angioedema, headache, hypertension, puritus, uticaria, rash and vomiting
Ustekinumab (Stelara) MOA
Inhibits p40 subunit of the IL-12 and IL-23 cytokines.
IL-12 is also known as natural killer stimulatory factor or cytotoxic lymphocyte maturation factor. This cytokine is made up of a 40 kDA and a 35 kDA subunit—IL-12 p40 subunit is shared by IL-23.
• IL-23 plays an important role in inflammatory response
• In conjunction with other cytokines (IL-6, TGFβ) IL-23 stimulates naïve CD4+ T cells to differentiate into TH17 cells and TH22 cells, which are distinct from TH1 and TH2 cells.
TH17 cells promote the production of IL-17 which is a pro-inflammatory cytokine that enhances T cell priming and enhance the production of IL-1, IL-6, TNFα, and chemokines
Ixekizumab (Taltz) side effects
flu like symptoms, infection, pain at the site of injection, nausea, and oropharyngeal pain
Alirocumab (Praluent)
Human monoclonal antibody
Centuximab (Erbitux) side effects
immunogenecity, electrolyte depletion and infusion reactions
Nivolumab (Opdivo) MOA
It blocks immune checkpoint (immunologic brake) PD-1 (Programed death-1) (PD-1 receptor is present on T cells and B cells)
It blocks the activation of PD-1 receptors through their ligand, PD-L1–Binding of PD-L1 to PD-1 receptors causes the inhibition of T cells
PD-1, then allows the immune response to be produced in the closed vicinity of the tumor
Immune checkpoint—functions as a negative feedback for immune response (downregulate immune response)
Inhibit T cell function in secondary lymphoid organs and enhance the function of regulatory T cells
Antibody itself is not treating the disease—it is inhibiting the immune checkpoint to allow the immune response to continue without any inhibition
Belimumab (Benlysta) side effects
nausea, diarrhea, fever, hypersensitivity, and infusion-site reactions, increased risk of infection
Belimumab (Benlysta)
Human monoclonal antibody
MOA of Alirocumab (Praluent)
Inhibits PCSK9 which will inhibit degradation of LDL receptors and increase removal of LDL cholesterol from circulation
Vedolizumab(Entyvio)
Humanized antibody
Infliximab (Remicade) side effects
Infection, cough, back pain, nausea, vomiting
Reslizumab (Cinqair) therapeutic uses
Severe asthma and the eosinophilic phenotype (latest onset and very severe)
NOT used for an acute asthma attack
Adalimumab (Humira) side effects
Infections, neurologic events and malignancies
Ipilimumab (Yervoy) therapeutic uses
Malignant melanoma
Adalimumab (Humira)
Human antibody
Alirocumab (Praluent) therapeutic uses
second line treatment to reduce LDL cholesterol levels and used in patients who do not respond well to diet, exercise, statins or are intolerant to statins
zumab
Humanized (human like) or CDR grafted antibody
Abciximab (Centorex, Reopro)
Chimeric monoclonal antibody
Vedolizumab(Entyvio) side effects
Flu like symptoms, GI problems, liver dysfunction, pain and swelling
Reslizumab (Cinqair) MOA
Inhibits IL-5
IL-5 is responsible for the proliferation, maturation, differentiation, and effector function of eosinophils)
Golimumab (Simponi) CI with what other drugs
abatacept
kineret
other TNFα blockers
Trastuzumab (Herceptin) MOA
Binds to human epidermal growth factor type 2 receptor protein (HER-2). HER are transmembrane tyrosine kinase receptors involved in cell growth, differentiation and proliferation of epithelial cells and cytoblasts
mutation in the HER-2 receptor causes an increased amount of the growth factor receptor protein on the tumor cell surface which increases proliferation of the cells
inhibits the proliferation of tumor cells over expressing HER-2–causes HER-2 receptor down regulation by binding to the receptor and causing endocytosis of some receptors as well as limiting the signal for cell growth.
Fc region causes lysis via antibody-dependent cell-mediated cytotoxicity
Bevacizumab (Avastin) therapeutic uses
In combination with a standard chemotherapeutic regimen (5-fuouracil-based) it is used for the treatment of patients with malignant colon or rectal cancer
Some forms of renal, ovarian, lung, and brain cancers
Rituximab (Rituxan) therapeutic uses
Non-Hodgkin’s lymphoma.
Fifty percent of the patients have responded to the treatment with full or partial remission
Alemtuzumab (Lematrada) therapeutic uses
multiple sclerosis and tissue transplantation
