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IP Oncology Exam 1 > Lec 4: Antibody - Based Cancer Therapies > Flashcards

Lec 4: Antibody - Based Cancer Therapies Flashcards

1
Q

Monoclonal Antibody Cancer Immunotherapy…

A

Monoclonal Antibody Cancer Immunotherapy is a
targeted therapy utilizing antigen-antibody interactions to target cancer cells.
.
NOTE: antibody vs small molecule? Antibody will active our immune system…and have a longer T1/2 than small molecules BUT it is more $$$

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2
Q

Antibody Basics

A
  • Glycoproteins (Immunoglobulin) produced by a plasma cell (Mature B-cell) in response to an antigen (foreign molecule).
  • Y-shaped protein
  • Bind specifically to a single antigen.
  • Secreted by a single B-cell (1 clone) vs polyclonal (produced by many B-cells).
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3
Q

The Fab region _____________.
a) Has a hypervariable region that binds with antibody.
b) Has a hypervariable region that binds with antigen.
c) Has a hypervariable region that binds with other immune cells.
d) Has a hypervariable region that binds with DNA.
e) All of the above.

A

B

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4
Q

Immunoglobulin Structure

A
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5
Q

Antigen-Antibody Interaction…what’s an antigen?

A
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6
Q

Humanization of Therapeutic Antibodies Has Reduced Their Immunogenicity and Lengthened Their Biological Half-Life

A

NOTE: omab and ximab is not really used anymore… people don’t really response to it.

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7
Q

Therapeutic Uses of Immunoglobulins. . . Treatment- many drugs currently in use are antibodies…in vivo and in vitro?

A

1.) Treatment- many drugs currently in use are antibodies.
— Bind soluble inflammatory cytokines (‘decoy receptors’) — Use to block cell surface receptors (unique receptors on tumor cells)
— Inhibit biological processes - angiogenesis
— Recruit immune effector cells
— Use to target specific cells for clearance or cell death
— Drug delivery system (get drug to site of action)
.
2.) In vivo diagnosis – Radiolabeled antibodies to detect metastatic tumors.
.
3.) In vitro diagnostic tests (ELISAs, Flow Cytometry)
.
NOTE: This is mainly the role of FaB region! (antibody binding to antigen!)

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8
Q

Therapeutic mAbs and their derivatives …

A

Therapeutic mAbs and their derivatives … can affect target cell function and viability via several different mechanisms…. NOTE: what Fc region can do!

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9
Q

Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

A
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10
Q

Function of C regions (Fc portion)

A
  • Activation of complement: IgM antibody, IgG1,3 Not IgG2 or IgG4
    .
  • Bind to Fc receptor of cell
    —- Opsonization, enhancement of antibody uptake by Dendritic Cells and Macrophages (IgG Not IgA or IgM)
    —- Recruitment of immune effector cells
    —- Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): IgG1,3 …Not IgG2 or IgG4
    —- Participation in type I hypersensitivity: IgE
    .
  • Passage through the placenta (IgG) and mucosa (IgA)
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11
Q

Monoclonal Antibodies for the Treatment of Metastatic
Colon Cancer

A
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12
Q

EGFR . . .

A

EGFR is a cell surface receptor frequently mutated or overexpressed in solid tumors such as lung, colorectal, and head and neck cancers.
.
Colon Cancer: 60 – 80%
Associated with poor prognosis…if something is wrong or mutated with the EGFR then it is bad/ detrimental because EGFR have a lot of different pathways.. more chances that something will go wrong.
.
Cetuximab
Panitumumab

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13
Q

Cetuximab and Panitumumab are both monoclonal antibody therapies used in Colon Cancer.
Cetuximab is an IgG1 antibody against murine EGFR. Panitumumab is an IgG2 antibody against human EGFR.
Which therapy would you predict would activate AntibodyDependent Cell-Mediated Cytotoxicity of the tumor cells?
a) Panitumumab
b) Cetuximab
c) Both Panitumumab and Cetuximab
d) Neither Panitumumab or Cetuximab

A

b) Cetuximab

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14
Q

EGFR inhibitors result in . . .

A

EGFR inhibitors result in inhibition of cell growth, induction of apoptosis, decreased matrix metalloproteinase secretion and reduced vascular endothelial growth factor…
.
Cetuximab
Panitumumab

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15
Q

EGFR inhibitors: Cetuximab (Erbitux)… indication, PK, side effects

A

Cetuximab (Erbitux) - IgG1 Monoclonal Antibody
against EGFR – Activation of ADCC
.
Indications: Metastatic Colorectal Cancer (KRAS/NRAS Wild-Type)
.
Pharmacokinetics: FYI
- IV Infusion
- ½ Life: 4.75 Days
.
Side Effects: Adverse Skin Reactions, Infusion Reactions,
Hypomagnesemia, Respiratory (Dyspnea and Cough), Liver Toxicity, Neutropenia, Infections

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16
Q

EGFR inhibitors: Panitumumab (Vectibix)… indication, PK, side effects

A

Panitumumab (Vectibix) - IgG2 Monoclonal Antibody
against EGFR
.
Indications: Metastatic Colorectal Cancer (KRAS/NRAS Wild-Type)
.
Pharmacokinetics: FYI
- IV Infusion
- ½ Life: 7.5 Days
.
Side Effects: Adverse Skin Reactions, Hypomagnesemia,
Respiratory (Dyspnea and Cough)

17
Q

VEGF Inhibitors - general MOA and drugs we will talk about

A

VEGF Inhibitors inhibit tumor cell growth through lack of
nutrients and hypoxia.
.
Bevacizumab (Avastin)
Ramucirumab (Cyramza)
.
NOTE: During angiogenesis (formation of new blood vessels), VEGF helps stimulate the formation of new blood vessels to supply the tumor with oxygen and nutrient! This is bad because it helps the cancer cell growth! VEGF inhibitors stops this process!

18
Q

VEGF Inhibitors: Bevacizumab (Avastin) . . .indication, PK, Side effects, DI

A

Bevacizumab (Avastin) – IgG1 Monoclonal antibody
against VEGF-A
.
Indication: Treatment of Metastatic Colorectal Cancer
.
Pharmacokinetics:FYI
- IV Infusion
- ½ Life: 20 Days
.
Side Effects: Neutropenia and Infections, Infusion Reactions, Hypertension, Peripheral Edema, Venous Thromboembolisms, Nausea, Diarrhea
.
Drug Interactions: Anthracyclines (Cardiotoxic Effects),
Bisphosphonates (Risk of Osteonecrosis of Jaw)

19
Q

VEGF Inhibitors: Ramucirumab (Cyramza) . . .indication, PK, Side effects, DI

A

Ramucirumab (Cyramza) – IgG1 Monoclonal antibody
against VEGFR2
.
Indication: Treatment of Metastatic Colorectal Cancer
.
Pharmacokinetics: FYI
- IV Infusion
- ½ Life: 14 Days
.
Side Effects: Peripheral Edema Neutropenia, Hypertension, Proteinuria, Wound Dehiscence, Nausea, Diarrhea, Hypocalcemia
.
Drug Interactions: Bisphosphonates (Risk of Osteonecrosis of Jaw)

20
Q

The tumor microenvironment is composed of both “protumor” and “anti-tumor” promoting immune cells … know the general

A
21
Q

Immune Checkpoint Inhibitors: Activate Cytotoxic T-cells to Kill Cancer Cells…what are the two main mech? what are the receptors we are targeting?

A
22
Q

Immune Checkpoint Inhibitors… MOA and info

A

Immune Checkpoint Inhibitors: Activate
Cytotoxic T-cells to Kill Cancer Cells.
.
Nobel Prize for Medicine in 2018!! won by James Allison and Tasuku Honjo

23
Q

What’s significant about PD-1 and PD-L1 and what monoclonal antibody will we be talking about?

A

PD-1 is an “off switch” on cytotoxic T-cells. PD-1 or PD-L1
antibodies boost the immune response against cancer cells by activating cytotoxic T-cells.
.
Nivolumab (Opdivo)
Pembrolizumab (Keytruda)

24
Q

Nivolumab (Opdivo) – IgG4 Monoclonal antibody against PD-1 . . . indication, PK, SE, DI

A

Nivolumab (Opdivo) – IgG4 Monoclonal antibodyagainst PD-1
.
Indications: Treatment of Metastatic Colorectal Cancer (dMMR/MSI-H)
.
Pharmacokinetics:
- IV Infusion
- ½ Life: 25 Days
.
Side Effects: Edema, Hypertension, Skin Rash, Pruritus, Hyperglycemia,
Hyponatremia, Increased serum triglycerides, Increased liver enzymes,
Infection
.
DI??

25
Q

Pembrolizumab (Keytruda) – IgG4 Monoclonal antibody PD-1. . . indication, PK, SE, DI

A

Pembrolizumab (Keytruda) – IgG4 Monoclonal antibody PD-1Indications: Treatment of Metastatic Colorectal Cancer (dMMR/MSI-H)
.
Pharmacokinetics:
- IV Infusion
- ½ Life: 22 Days
.
Side Effects: Edema, Cardiac Arrhythmia, Skin Rash, Pruritus,
Hyperclycemia, Hyponatremia, Increased serum triglycerides,
Increased liver enzymes, Infection
.
Drug Interactions: Immunosuppressants – Diminish therapeutic effect

26
Q

Ipilimumab (Yervoy) – IgG1 Monoclonal antibody against CTLA-4. . . indication, PK, SE, DI

A

CTLA-4 is a negative regulator of T-cell function. Blockade of CTLA-4 can
induce the regression of tumors through activation and proliferation of
anti-tumor cytotoxic T-cells.
.
Ipilimumab (Yervoy) – IgG1 Monoclonal antibody against CTLA-4
.
Indications: Treatment of Metastatic Colorectal Cancer (dMMR/MSI-H)
.
Pharmacokinetics:
- Intravenous Infusion
- ½ Life: 15 days
.
Side Effects: Skin Rash, Pruritus, Diarrhea, Nausea,
Decreased hemoglobin, Anemia, Increased liver
enzymes, Cough, Dyspnea
.
Drug Interaction: Vemurafenib – BRAF Inhibitor
(Enhance hepatotoxicity)

27
Q

Clinical data indicate an association between prior antibiotic treatmentand response to Immune Check Point Inhibitors… Hypothesis:

A

Hypothesis: Gut microbe stimulation is necessary for Immune Checkpoint Inhibitor function (Antigen Presentation).
.
NOTE: No prior abx to immune checkpt inhibitors = better chances of survival and better chances that the body will positively react to the treatment!… Prior abx is bad! and will decrease survival! WHY? abx kills the good bacteria…good gut bacteria/ microbiome is necessary for immune check point to have proper performance!

28
Q

Emerging Trends in Treatment of Metastatic Colon Cancer

A
29
Q

CAR T-cell Therapy

A

CAR T-cell Therapy – Cytotoxic T-cells are genetically engineered
to produce TCR receptors that recognize tumor cell surface
antigens to initiate killing of those cancer cells .

30
Q

Which of the following monoclonal antibodies is an immune
checkpoint inhibitor?
a) Panitumumab
b) Bevacizumab
c) Nivolumab
d) Adalimumab

A

C.

31
Q

Which of the following monoclonal antibodies is a VEGF
inhibitor?
a) Panitumumab
b) Bevacizumab
c) Nivolumab
d) Adalimumab

A

B.

32
Q

Which class of monoclonal antibodies has the lowest risk of
immunogenicity?
a) -omab
b) -ximab
c) -umab
d) -ixab
e) -zumab

A

C.

IP Oncology Exam 1 (4 decks)

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