Monoclonal Antibodies Flashcards
What part of the antibody recognizes a unique antigen?
tips of the Y; fragment-antigen binding (Fab) variable region
How does an antibody bind an antigen with absolute precision?
tips of the Y contain a paratope that is specific for one particular epitope on an antigen
What two things can antibodies do after binding to an antigen?
- tag a specific target cell for attack by the immune system
- directly neutralize the specific target cell
Which region of the antibody allows it to communicate with other components of the immune system?
the base of the Y; Fc constant region
How can antibodies recognize a wide variety of antigens?
diversity of paratopes within antigen-binding fragments
What are monoclonal antibodies?
antibodies made by identical immune cells that are clones to a unique parent cell
What does it mean for an antibody to have monoclonal affinity?
the antibody specifically recognizes the same epitope
What are the main types of monoclonal antibodies?
- murine
- chimeric
- humanized
- human
What type of antibody is -Omab?
entirely derived from mouse
What problems occur with murine antibodies?
- allergic reactions
- quickly eliminated from the body
What type of antibody is -XImab?
variable Fab region is mouse; constant Fc region is human (about 70%)
How does having a mostly human antibody improve its effects?
less likely to trigger immunogenic/allergic response
What type of antibody is -ZUmab?
85-90% human; hypervariable region is mouse
What type of antibody is -Umab?
100% human
What is true of all monoclonal antibodies regardless of how much human source they have?
can still cause allergic reaction
What are some ways monoclonal antibodies are used to treat cancer?
- inhibit cancer cell growth/division
- bind specific sites on cancer cells to cause death
- conjugates/attached to cytotoxic anticancer drugs or radioactive compounds
- activate human immune system to destroy cancer cells
What does substem A tell you about monoclonal antibodies?
specifies the target (tumor, bacteria, etc)
What does substem B tell you about monoclonal antibodies?
specifies the amino acid sequence source from which the monoclonal antibody is derived
Why are all monoclonal antibodies given IV?
mostly peptide-based drugs with poor oral absorption
What types of infusion-related reactions are seen with monoclonal antibodies?
- hypersensitivity
- anaphylaxis
- hypotension
- bronchospasm
- death
What is used for pre-medication to prevent infusion-related reactions?
glucocorticoid receptor agonists; histamine receptor antagonists
What type of agents are associated with additional side effects?
conjugated/attached to cytotoxic anticancer drugs
What type of side effects are associated with agents that activate the human immune system?
potentially life-threatening autoimmune side effects
What are tumor biomarkers that monoclonal antibodies target?
tumor Growth Factors;
Growth Factor Receptors
How does Bevacizumab inhibit angiogenesis?
binds to VEGF-A and prevents it from properly interacting with its VEGFR-2 receptor
What side effects are associated with Bevacizumab?
- inhibition of blood vessel growth –> HTN and proteinuria
- hemorrhage (bleeding)/ thrombosis (clotting)
- decreased blood flow –> impaired wound healing
When should Bevacizumab NOT be administered?
28 days before or after surgery due to impaired wound healing
What is Bevacizumab used to treat?
Solid tumors (colon cancer)
Non-small cell lung cancer
What must be over-expressed for Trastuzumab to be used?
HER2 overexpression is required
Which portion of the mab binds to HER2+ tumor cells and marks them for destruction by the immune system?
Fc
Which portion of the mab prevents downstream HER2 signaling and dimerization to inhibit proliferation of cells?
Fab
What is the major toxicity associated with Trastuzumab?
cardiotoxicity; Herceptin mediated destruction of cardiomyocytes
What must be monitored at baseline and during treatment with Trastuzumab due to cardiotoxicity?
LVEF
How is LEVF monitored when using Trastuzumab?
echocardiogram- ultrasound
MUGA scan- radioactive tracer
For biologic EGFR inhibitors to be effective, what pharmacogenomic tests must be done?
- EGFR + expression
- KRAS wild type
EGFR inhibitors cannot be used if what mutation is present?
KRAS mutation
What is a side effect that any EGFR inhibitor can cause and indicates better clinical response?
rash
What can be given for prophylaxis/ treatment to reduce skin damage from EGFR inhibitor-induced rash?
- topical emollients
- glucocorticoids
- antibiotics
What are patient counseling points for EGFR inhibitors?
- avoid sunlight
- use sunscreen/ cover up
What are the 3 MOAs of Rituximab?
- complement-dependent cytotoxicity
- apoptosis
- antibody-dependent cell-mediated cytotoxicity
What must be positive to use Rituximab?
B-cell antigen CD20
Why is CD20 absent on lymphoid stem cells?
allows the body to produce a new healthy B cell population
By non-selectively destroying B cells, what happens when healthy B cells are destroyed?
bone marrow suppression –> increased infection risk
What is the natural “brake” receptor on T cells?
PD-1 (Programmed cell Death -1 receptor protein)
What is the “brake” receptor on cancer cells?
PD-L1 (Programmed cell Death-Ligand 1 receptor protein)
What is the result of PD-1 and PD-L1 interaction?
T cell cannot recognize/ kill the cancer cell
What is the result of Keytruda/ Opdivo binding to the PD-1 receptor on the T cell?
T cell releases distinct chemicals to kill the cancer cell
What side effects are associated with blocking the immune systems “brake”?
- drug-induced autoimmune disease
- potentially life-threatening immune-mediated reactions (colitis, hepatic toxicity, thyroid dysfunction, myocarditis)
What medication targets CTLA-4 break receptor on the T cell?
Ipilimumab (YEROVY)
