PHRM 835 Exam 2 Biologics Flashcards
biologics are generally derived from ?
living material
IgG accounts for what percent of naturally occurring antibodies?
75-80%
two Fc receptors to know
Fcyr (Fc gamma R)
FcRn (neonatal FcR)
targets of monoclonal antibodies are found where? (2 places)
-on cell membrane (ex. Herceptin)
-circulating in the blood (ex. infliximab; TNFa antibody)
mAb’s cannot be taken through which route?
orally
mAb major absorption pathway
by convective flow of the interstitial fluid into lymphatic capillaries into lymphatic channels
mAb minor absorption pathway
diffusion through interstitial fluid and transport across blood capillary
the mAb minor absorption pathway is for
a. small proteins
b. big proteins
a. small proteins
(< 5 kD size)
which is faster, blood flow rate or lymph flow rate?
blood flow rate
(lymph flow rate is 100-500 times slower)
where does lymph drain into?
blood circulation (systemic)
mAbs are mainly eliminated through _____ _____
proteolytic degradation
what process extends IgG half-life?
pinocytosis by endothelial cells involving FcRn (IgG recycling)
two mAb clearance pathways
nonspecific and specific clearance pathways
what is the nonspecific clearance pathway for mAbs?
proteolysis by reticuloendothelial system (RES)
what is the specific clearance pathway for mAbs?
target mediated disposition (elim. of mAbs through its antigen-specific interactions)
the nonspecific clearance pathway is
a. dose-independent
b. dose-dependent
a. dose-independent
(therapeutic mAb concentration is below endogenous IgG level 10 mg/mL)
the specific clearance pathway is
a. dose-independent
b. dose-dependent
b. dose-dependent
(antibody binding to the target antigen can be saturated)
how does the reticuloendothelial system work?
immune cells bind to Fc region of antibody -> receptor-mediated endocytosis -> degradation in lysosome
example of drug in class that uses specific clearance pathway
Efalizumab
what is Efalizumab used to treat?
psoriasis
high dose Efalizumab has ___ elimination
a. rapid
b. slow
b. slow
low dose Efalizumab has ___ elimination
a. rapid
b. slow
a. rapid
mAB immunogenecity: what does it means?
increased fraction of nonhuman sequence in the molecule leads to more immune response
(mouse <- chimeric <- humanized <- human)
which has the most immunogenecity?
a. abciximab
b. adalimumab
c. muromonab
d. daclizumab
c. muromonab
absorption of mAbs is mainly through _____ uptake due to their large molecular size
lymphatic
true or false: Cytochrome P450 enzymes in the liver play critical roles in elimination of monoclonal antibodies
false
true or false: Oral route is the preferred route of administering biologics
false
true or false: Genetic engineering of Fc portion of mAb for better binding affinity to FcRn is expected to increase mAb half-life
true
true or false: Ranibizumab is Fab fragment of antibody targeting VEGF (vascular endothelial growth factor) while bevacizumab is a full-sized antibody. Clearance of ranibizumab is expected to be shorter than that of bevacizumab
true
(no Fc so doesn’t bind to FcRn -> antibody elim will be really fast)
True or false: After months of infliximab (mAb against TNFa) treatment for a patient with inflammatory bowel disease, anti-infliximab antibodies are detected. The elimination rate of infliximab is expected to increase as compared to the beginning of therapy
true
true or false: Antidrug antibodies (ADA) against mAb typically increase both the elimination rate and the efficacy of mAb
false
(it does increase elim rate but efficacy will decrease)
true or false: mAb engineering for increased binding to FcRn can increase the mAb half-life
true
(M252Y/S254T/T256E mutations on motavizumab led to a 10-fold increase in FcRn affinity and significantly increased its half-life)
true or false: mAb engineering for enhanced binding to FcyR (Fc gamma R) can improve potency
true
(Anti-CD20 antibody, obinutuzumab and ocrelizumab, show enhanced FcgR binding affinity and greater potency compared to a first-generation antibody, rituximab)
