035 Antibody targeted cancer therapy Flashcards
Where the Fv region variable?
4 variable regions on the amino terminal part recognizes antigens.
Where are cdr regions located?
3 on each heavy and light chain on each Fv region, which are hypervariable and bind to antigen.
What are chimeric antibodies
Entire V regions of mouse grafted onto human constant regions.
What are humanized antibodies?
CDR mouse regions grafted onto human V regions
What is a full human anybody?
Human IgG genes completely
Which receptor binding will cause complement dependant cascade?
C1q region
Which receptor binding will cause ADCC binding cascade?
FCYR region –> NK cells
What does Fc binding with FcRn result in?
Increased half life
How does FcRn extend circulatory half life of antibody?
FcRn region recognized by endothelium cells and taken up by endosomes. It binds to receptor and held tight in low pH 6.0 endosomes rather than being broken down in endosomes. These endosomes bring the antibody back to epithelium and released at 7.4.
What is rituximab used for and how does it work?
Rituximab targets CD20 on both normal and malignant B cells, but do not affect plasma or immature B cells.
What is trastuzumab used for?
Anti-HER2
How do antibody drug conjugates work
ADC taken up by early endosomes to lysosomes
Lysosomes –> internal conditions causing cytotoxic component dissociate and circulate freely in cytoplasm.
These cause intercalation or disrupt microtubule formation.
What are engineered single chain Fv antibody fragments?
When the heavy and light Fv regions are tethered together into a single polypeptide strand by a flexible linker. The ScFv is reformatted into IgG antibodies to recruit T-cells.
What is blinatumomab and how does it work?
These are BiTE cells in which one variable domain of the ScFv region binds to tumor antigen, and the other binds to immune cell. This acts as a bridge between immune cell and tumor cells. Blinatumomab targets CD19 on B - cells: non hodgkins lymphoma.
Explain how CART cells work?
T cells are removed from patient and modified to xpress receptors specific to form of cancer. scFv part recognizes tumor cells. Inside, there is CD28 and CD3Z to produce attack on T cells.
