Test 2 MABs Flashcards
structure of antibody
- 2 heavy chains: 50kD
- 2 light chains: 25kD
- connected via disulfide bond @ hinge region
CDR
- hyper-variable region
- antigen binding site
Which cells make antibodies?
B-cells
murine Ab
- complete mouse
- omab
chimeric Ab
- mouse FAB, human Fc portion
- ximab
humanized Ab
- mainly human; some mouse
- zumab
fully humanized Ab
- completely human
- umab
What was the effect of the humanized Ab?
adverse reactions went from 50% to 0.1-34%
papain
digest Ab into Fab and Fc portions
pepsin
digest Ab into (Fab)2 and Fc portion into small fragments
scFv
- variable regions joined together via peptide linkage
- smallest in Ab production that we have reached
Where are Bcells located?
spleen
Hybridoma
B cells fused with myeloma cells to produce antibodies indefinitely
production of MAb
- in vitro manipulation
- introduction into plasmid
- transfer into myeloma cell
- expand growth into tissue culture or mouse for production
Results of interaction of mAb with a cell receptor
- Direct modulation of target antigen
- Cell damage
Direct modulation of target antigen
- Agonism
- Antagonism
Agonism
mimic the activity of the antigen or receptor
Antagonism
inhibit the activity of the antigen or receptor
types of cell damage
- complement
- antibody dependent cell-mediated cytotoxicity
example of agnosim action in cancer
induction of activity of antigen / receptor that causes cell death
example of antagonism action in cancer
- blocking factor that promotes cancer cell growth
- Herceptin
Complement-dependent cellular cytotoxicity
- complement on cell surface
- conformational change
- membrane attack complex (MAC) formed
- disrupts cell membrane
- cell death
Antibody-dependent cell-mediated cytotoxicity
- Ab binds to antigen on target cell
- NK cells recognize the Fc portion of those Ab and they bind
- NK cells activated
- perforin and granzyme released
- cell lyses
Alemtuzumab
- Campath
- binds to CD52
- kills cell via Ab and complement-mediated cellular cytotoxicity
Bevacizumab
binds to VEGF and prevent its interaction with its receptors
VEGF
promotes growth of vessels / vascular system to provide nutrients to the tumor
EGF
promotes cell proliferation
Panitumumab
bind to EGFR to inhibit cell growth
Cetuximab
bind to EGFR to inhibit cell growth
Rituximab
- binds to CD20
- Ab and complement-mediated cytotoxicity
Trastuzumab
- binds to HER2 protein
- Ab-mediated cytotoxicity and immune cell activation
Radioimmunoscintigraphy
- Diagnostic applications of Radiolabeled antibodies
- can be used for cancer, infection, and angiogenesis
Radioimmunotherapy
- Therapeutic applications of Radiolabeled antibodies
example of
radiolabeled antibody used for therapy
- Yitrium (Y90) recognizes CD20 in target B tumor cell
- radiation released by Y90 penetrates and damages cell
