Antibody Based Cancer Treatment Flashcards
1
Q
Antibody Basics
A
- Glycoproteins (Ig) produced by a plasma cell in response to an antigen
- Y-shaped
- Binds tightly and specifically to single antigen
- Secreted by a single B-cell vs polyclonal
2
Q
Ig Structure
A
- Heavy chains are distinct for each of the five classes
- Gamma, mu, alpha, beta, and delta
- 3-4 Beta-sheets when folded
3
Q
Antigen
A
- Any agent capable of eliciting an immune response
- Often a protein or carb
- Isolated molecules
- On surface of cell or virus
4
Q
Antigen-Antibody Interaction
A
- Specific antibody molecule will recognize one specific Epitope-Peptide Sequence of an antigen
- One antibody produced by single B-cell
- Antibody-antigen interaction is very strong
- Hypervariable region determines the binding specificity
5
Q
% Human + Name/Half Life
A
- Omab - 0% human
- Ximab - 65% human
- Zumab - >90% human
- Umab - 100% human
-Half life increases with % human
6
Q
Uses of Ig
A
- Bind soluble inflammatory cytokines (decoys)
- Block cell surface receptors (tumor cells)
- Target specific cells for clearance
- Drug delivery system
- In vivo diagnosis - radiolabeled antibodies to detect metastatic tumors (ELISAs, flow cytometry)
7
Q
Function of C Regions
A
- Activate complement - IgM and IgG1
- Bind to Fc receptors of cells - opsonization (enhanced uptake by dedritic cells/macrophages), ADCC, (IgG1 and 3), Type I allergic rxn (IgE)
- Passage through placenta (IgG) and mucosa (IgA)
8
Q
EGFR Receptor
A
- Frequently mutated or overexpressed in solid tumors (lung, colon, head/neck)
- Colon cancer: 60-80%, poor prognosis
- Cetuximab or Panitumumab
- Inhibitors stop cell growth, induce apoptosis, decrease matrix metalloproteinase secretion and reduce vascular endothelial growth factor
9
Q
Cetuximab
A
- Erbitux
- IgG1 monoclonal antibody for EGFR
- Used in metastatic colorectal cancer (KRAS/NRAS Wild-type)
- IV infused
- 1/2 Life: 4.75 days
- SE: Skin/infusion reactions, hypomagnesemia, respiratory issues, liver tox, neurtopenia, infections
10
Q
Panitumumab
A
- Vectibix
- IgG2 antibody against EGFR
- Used in metastatic colorectal cancer (KRAS/NRAS Wild-type)
- IV infused
- 1/2 Life: 7.5 days
- SE: adverse skin rxns, hypomagnesemia, respiratory difficulty
11
Q
VEGF Inhibitors
A
- Inhibit tumor cell growth through lack of nutrients and hypoxia
- Bevacizumab and Ramucirumab
12
Q
Bevacizumab
A
- Avastin
- IgG1 antiboy against VGEF-A
- Used in metastatic colorectal cancer
- IV infused
- 1/2 Life: 20 days
- SE: Neutropenia infections, infusion rxn, HTN, peripheral edema, VTE, nausea, diarrhea
- Drug Interactions: Anthracyclines (cardiotox.), bisphosphonates (osteonecrosis of jaw)
13
Q
Ramucirumab
A
- Cyramza
- IgG1 antibody against VEGFR2
- Used in metastatic colorectal cancer
- IV infused
- 1/2 Life: 14 days
- SE: peripheral edema, neutropenia, HTN, proteinuria, wound dehiscence, nausea, diarrhea, hypocalcemia
- Drug interactions: Bisphosphonates (osteonecrosis of jaw)
14
Q
PD-1
A
- “Off-switch” on cytotoxic T-cells
- PD-1 or PD-L1 antibodies boost immune response against cancer cells by activating cytotoxic T-cells
- Nivolumab or Perbrolizumab
- Interact with immunosuppressants (diminish effects)
15
Q
Nivolumab
A
- Opdivo
- IgG4 antibody against PD-1
- Used in metastatic colorectal cancer (dMMR/MSI-H)
- IV infused
- 1/2 Life: 25 days
- SE: Edema, HTN, skin rash, pruritus, hyperglycemia, hyponatremia, increase serum triglycerides, increased liver enzymes, infection
