Antineoplastics: Antibodies and Cytokine therapy Flashcards
The two major types of targeted tumor therapy are __ that bind extracellularly and __ that target intracellular kinases and growth factors/GF receptors
The two major types of targeted tumor therapy are monoclonal antibodies that bind extracellularly and small molecule inhibitors that target intracellular kinases and growth factors/GF receptors
Targeted tumor therapy exploits the concept of non-specific immune stimulation. Describe this 2 - step concept
Basically you start by injecting molecules that’ll bind to the tumors and “activate” them, then the tumors will release cytokines that alert T cells and other immune cells that then become activated and kill the tumor cell
Monoclonal antibodies primarily have 4 mechanisms of action. Describe each.
Antibodies can crosslink w/ antigen >> apoptosis
Induce antibody dependent cytotoxicity
Initiate complement dependent cytotoxicity
Neutralize angiogenic factors
In general, there are 4 types of monoclonal antibodies: murine derived, chimeric, humanized and fully human. Which of these is more likely to cause hypersensitivity reactions?
There’s a risk of hypersensitivity reactions with monoclonal antibodies but in general, the risk is higher with the more foreign antibodies and less so with more humanized ones (so higher risk with mouse and chimeric abs, compared to others)
Fill in the blanks (which prefix goes with what type of antibody?)
Some antibodies are conjugated to other molecules to increase cytotoxic effects. Describe how conjugated monoclonal antibodies work
The conjugated antibodies are antibodies specific to a tumor/tumor antigen and are connected to a cytotoxic agent via a linker molecules
When internalized by the tumor cell, the cytotoxic agents are released and cause apoptosis
**Since the cytotoxic agents can also be microtubule inhibitors, peripheral neuropathy is one of the side effects**
**note that examples of cytotoxic agents are DNA disruptors or microtubule inhibitors**
The most common side effect of antitumor antibodies is ___
CD20-targeting antibodies like Rituximab generally cause which side effect(s)?
The most common side effect of antitumor antibodies are infusion reactions (e.g. shake and bake chills etc)
CD20-targeting antibodies like Rituximab can lead to tumor lysis syndrome and cytokine release syndrome. Also leads to myelosuppression + increased risk of infection
**can address effects of infusion reactions with acetaminophen, diphenhydramine, steroids**
Myelosuppression and increased risk of infection are common side effects of CD20 antibodies, as well as what two other abs? (hint: they’re -zumab-s)
Myelosuppression and increased risk of infection are common side effects of CD20 antibodies, as well as alemtuzumab, elotuzumab
Her-2 targeting antibodies can lead to what side effect?
Congestive heart failure (just remember heart-2)
___ targeting antibodies commonly cause dermatologic toxicities, mainly manifesting as acneiform rash
EGF-R targeting antibodies commonly cause dermatologic toxicities, mainly manifesting as acneiform rash
**know that EGF-R is all over the skin so naturally you would have skin reactions**
**can be addressed w/ tetracyclines + other antibiotics commonly used for acne**
The most common VEGF inhibitor is ___ (hint: B_V_)
Describe the mechanism of action of VEGF inhibitors
The most common VEGF inhibitor is BeVacisumab
Bevacizumab blocks VEGF-R >> prevents VEGF binding to its receptor >> no angiogenesis (so no blood supply to the tumor)
**also in this class is Ramucirumab**
Describe the difference between cytokine therapy and immune checkpoint inhibitors
Cytokine therapies: essentially giving exogenous cytokines that can activate immune cells to kill tumor cells
Immune checkpoint inhibitors basically enhance T cell’s ability to kill tumor cells by inhibiting proteins that would normally regulate the T cell’s ability to kill things (proteins such as PD1 and CTLA4)
What are the 2 classes of checkpoint inhibitors and what drugs are in this class?
Nivolumab/Pembrolizumab: anti-PD1 antibodies (anti programmed cell death receptor)
Ipilimumab: anti-CTLA4 antibody
Describe the mechanism of action of checkpoint inhibitors
Recall from immunology that CTLA4 and PDL-1 are basically cell death receptors/immune function regulators. Infected cells/weird cells like cancer cells can express ligands for these proteins, thereby rendering the T cells unable to kill off the cells.
In this case, we’re stopping that process and allowing for the T cells to recognize the tumor antigens, become activated and proceed with killing the tumor cell (where it otherwise wouldn’t if we didn’t have the checkpoint inhibitor)
Which organ systems are primarily affected by immune checkpoint inhibitors/what side effects are observed when using immune checkpoint inhibitors?
Skin: rash, pruritis
Liver: hepatotoxicity
GI: diarrhea, colitis
Thyroid: hypophysitis
What is the mechanism of action of Imatinib and other drugs in its class?
In which (blood) tumor is this class of drugs indicated?
Imatinib (and dasatinib) inhibit Bcr-Abl kinase (and c-kit, which is in GI stromal tumors)
Indicated in CML
___ is an EGFR tyrosine kinase inhibitor that is indicated in non small cell lung cancer + pancreatic cancer
Erlotinib is an EGFR tyrosine kinase inhibitor that is indicated in non small cell lung cancer + pancreatic cancer
Fill in the blanks
2 drugs that are predominantly VEGFR inhibitors (and have other targets) and are indicated in renal cell carcinoma are ___
2 drugs that are predominantly VEGFR inhibitors (and have other targets) and are indicated in renal cell carcinoma are sorafenib and sunitinib
What are the side effects of sunitib and sorafenib?
They’re both VEGFR inhibitors so need to think about hemorrhage, thromboembolism, compromised wound healing, hypertension (same as Bevacizumab)
Ibrutinib is a chronic lymphocytic leukemia drug that works by targeting ___
Ibrutinib is a chronic lymphocytic leukemia drug that works by targeting Bruton’s Tyrosine Kinase (BTK) in B cell malignancies
*drugs ending in -brutinib*
