(10) Antibody Drugs Flashcards
Review how monoclonal populations are grown
Review how monoclonal populations are grown
T or F: treatment of a patients of a patient with antibodies from a non-human source more than once is a bad idea
True
What are hybridomas?
- how are they humanized?
- Antibodies whose specificities on the variable heavy and light chains is created in an animal.
- We then remove the constant domains and add HUMAN constant domains to prevent the body from attacking the proteins
What was the problem with monoclonal antibody drugs (mAbs) that were 100% murine?
- side effects?
- They were recognized by human anti-mouse antibodies (HAMA) that removed the drug after 2-4 weeks (once aquired response could be mounted)
- on second treatment the drug was gone in 2-4 days (memory response)
- Side effects were still generally mild and could be treated with corticosteroids
What is the threshold of anti-drug antibody sites that can be on mAb drug before pharmacokinetics are drastically changed?
3 or more sites then the drug was much more rapidly eliminated
What is the half-life of new mAb drugs?
20 days
- This matches the amount of time endogenous IgG stays in the bloodstream
What makes the mAb drugs stay in the blood so long?
- FcRn (fetal domain is attached)
- they are now more humanized
How can mAbs be administered?
IV, SC (subcutaneous), or IM
What must you do to administer mAbs SC or IM?
Must use several small injections
**Absorption occurs via the lymphatic system
What is the major determinant of whether antimorals will be effective?
There ability to penetrate into solid tumors
**Removing portions of Fc and IgG have improved penetrance
What prevents mAbs from being broken down by CYPs?
They are too big and they are sometime formulated (with PEG) to prevent Renal Excretion
If mAbs aren’t broken down by CYPs, then how are they broken down?
By lysosomal cytosolic processes
T or F: Drug-Drug interactions are common with mAbs
False, no drug-drug interactions have yet been reported
