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Oncology > Monoclonal Antibodies > Flashcards

Monoclonal Antibodies Flashcards

1
Q

What part of the antibody recognizes a unique antigen?

A

tips of the Y; fragment-antigen binding (Fab) variable region

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2
Q

How does an antibody bind an antigen with absolute precision?

A

tips of the Y contain a paratope that is specific for one particular epitope on an antigen

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3
Q

What two things can antibodies do after binding to an antigen?

A
  1. tag a specific target cell for attack by the immune system
  2. directly neutralize the specific target cell
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4
Q

Which region of the antibody allows it to communicate with other components of the immune system?

A

the base of the Y; Fc constant region

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5
Q

How can antibodies recognize a wide variety of antigens?

A

diversity of paratopes within antigen-binding fragments

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6
Q

What are monoclonal antibodies?

A

antibodies made by identical immune cells that are clones to a unique parent cell

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7
Q

What does it mean for an antibody to have monoclonal affinity?

A

the antibody specifically recognizes the same epitope

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8
Q

What are the main types of monoclonal antibodies?

A
  1. murine
  2. chimeric
  3. humanized
  4. human
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9
Q

What type of antibody is -Omab?

A

entirely derived from mouse

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10
Q

What problems occur with murine antibodies?

A
  1. allergic reactions
  2. quickly eliminated from the body
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11
Q

What type of antibody is -XImab?

A

variable Fab region is mouse; constant Fc region is human (about 70%)

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12
Q

How does having a mostly human antibody improve its effects?

A

less likely to trigger immunogenic/allergic response

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13
Q

What type of antibody is -ZUmab?

A

85-90% human; hypervariable region is mouse

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14
Q

What type of antibody is -Umab?

A

100% human

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15
Q

What is true of all monoclonal antibodies regardless of how much human source they have?

A

can still cause allergic reaction

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16
Q

What are some ways monoclonal antibodies are used to treat cancer?

A
  1. inhibit cancer cell growth/division
  2. bind specific sites on cancer cells to cause death
  3. conjugates/attached to cytotoxic anticancer drugs or radioactive compounds
  4. activate human immune system to destroy cancer cells
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17
Q

What does substem A tell you about monoclonal antibodies?

A

specifies the target (tumor, bacteria, etc)

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18
Q

What does substem B tell you about monoclonal antibodies?

A

specifies the amino acid sequence source from which the monoclonal antibody is derived

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19
Q

Why are all monoclonal antibodies given IV?

A

mostly peptide-based drugs with poor oral absorption

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20
Q

What types of infusion-related reactions are seen with monoclonal antibodies?

A
  1. hypersensitivity
  2. anaphylaxis
  3. hypotension
  4. bronchospasm
  5. death
21
Q

What is used for pre-medication to prevent infusion-related reactions?

A

glucocorticoid receptor agonists; histamine receptor antagonists

22
Q

What type of agents are associated with additional side effects?

A

conjugated/attached to cytotoxic anticancer drugs

23
Q

What type of side effects are associated with agents that activate the human immune system?

A

potentially life-threatening autoimmune side effects

24
Q

What are tumor biomarkers that monoclonal antibodies target?

A

tumor Growth Factors;
Growth Factor Receptors

25
Q

How does Bevacizumab inhibit angiogenesis?

A

binds to VEGF-A and prevents it from properly interacting with its VEGFR-2 receptor

26
Q

What side effects are associated with Bevacizumab?

A
  1. inhibition of blood vessel growth –> HTN and proteinuria
  2. hemorrhage (bleeding)/ thrombosis (clotting)
  3. decreased blood flow –> impaired wound healing
27
Q

When should Bevacizumab NOT be administered?

A

28 days before or after surgery due to impaired wound healing

28
Q

What is Bevacizumab used to treat?

A

Solid tumors (colon cancer)
Non-small cell lung cancer

29
Q

What must be over-expressed for Trastuzumab to be used?

A

HER2 overexpression is required

30
Q

Which portion of the mab binds to HER2+ tumor cells and marks them for destruction by the immune system?

A

Fc

31
Q

Which portion of the mab prevents downstream HER2 signaling and dimerization to inhibit proliferation of cells?

A

Fab

32
Q

What is the major toxicity associated with Trastuzumab?

A

cardiotoxicity; Herceptin mediated destruction of cardiomyocytes

33
Q

What must be monitored at baseline and during treatment with Trastuzumab due to cardiotoxicity?

A

LVEF

34
Q

How is LEVF monitored when using Trastuzumab?

A

echocardiogram- ultrasound
MUGA scan- radioactive tracer

35
Q

For biologic EGFR inhibitors to be effective, what pharmacogenomic tests must be done?

A
  1. EGFR + expression
  2. KRAS wild type
36
Q

EGFR inhibitors cannot be used if what mutation is present?

A

KRAS mutation

37
Q

What is a side effect that any EGFR inhibitor can cause and indicates better clinical response?

A

rash

38
Q

What can be given for prophylaxis/ treatment to reduce skin damage from EGFR inhibitor-induced rash?

A
  1. topical emollients
  2. glucocorticoids
  3. antibiotics
39
Q

What are patient counseling points for EGFR inhibitors?

A
  1. avoid sunlight
  2. use sunscreen/ cover up
40
Q

What are the 3 MOAs of Rituximab?

A
  1. complement-dependent cytotoxicity
  2. apoptosis
  3. antibody-dependent cell-mediated cytotoxicity
41
Q

What must be positive to use Rituximab?

A

B-cell antigen CD20

42
Q

Why is CD20 absent on lymphoid stem cells?

A

allows the body to produce a new healthy B cell population

43
Q

By non-selectively destroying B cells, what happens when healthy B cells are destroyed?

A

bone marrow suppression –> increased infection risk

44
Q

What is the natural “brake” receptor on T cells?

A

PD-1 (Programmed cell Death -1 receptor protein)

45
Q

What is the “brake” receptor on cancer cells?

A

PD-L1 (Programmed cell Death-Ligand 1 receptor protein)

46
Q

What is the result of PD-1 and PD-L1 interaction?

A

T cell cannot recognize/ kill the cancer cell

47
Q

What is the result of Keytruda/ Opdivo binding to the PD-1 receptor on the T cell?

A

T cell releases distinct chemicals to kill the cancer cell

48
Q

What side effects are associated with blocking the immune systems “brake”?

A
  1. drug-induced autoimmune disease
  2. potentially life-threatening immune-mediated reactions (colitis, hepatic toxicity, thyroid dysfunction, myocarditis)
49
Q

What medication targets CTLA-4 break receptor on the T cell?

A

Ipilimumab (YEROVY)

Oncology (22 decks)

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