Final Exam Flashcards
Neoplasm
new growth, may be benign or malignant
Tumor
nonspecific term meaning lump or swelling
Cancer
any malignant neoplasm
Hyperplasia
increase in organ or tissue size due to an increase in the number of cells (BPH)
Metaplasia
an adaptive, substitution of one type of adult tissue to another type of adult tissue
Dysplasia
an abnormal cellular proliferation is which there is loss of normal architecture
Anaplasia
loss of structural differentiation, cells dedifferentiate (leiomyoma)
What is the epithelial origin of carcinoma?
neoplasm of squamous epithelial cell origin
What is the benign version of a carcinoma?
papilloma
What is the epithelial origin of an adenocarcinoma?
neoplasm of glandular tissue
What is the benign version of an adenocarcinoma?
adenoma
What is the epithelial origin of a sarcoma
neoplasm with origin in mesenchymal tissues or derivatives (bone, muscle, fat)
What is the epithelial origin of lymphoma and leukemia
hematopoietic tissues
What is the epithelial origin of melanoma?
cancer of pigment producing cells in the skin or the eye
What is the epithelial origin of a blastoma?
in precursor cells called blasts, which are more common in children
What is the epithelial origin of a teratoma?
germ cell neoplasm made of several different differentiated cell/tissue types
What cells are affected in myeloid leukemias?
common myeloid progenitor
What cells are affected in lymphocytic leukemias?
common lymphoid progenitor
What cells are affected in lymphomas?
small lymphocytes (T,B)
Cancer is characterized by what three things?
- uncontrolled cellular growth (benign,cancer)
- tissue invasion (cancer)
- metastasis (cancer)
What are the hallmarks of cancer?
- sustaining proliferative signaling
- avoiding immune destruction
- enabling replicative immortality
- activating invasion and metastasis
- inducing or accessing vasculature
- genome instability and mutation
- resisting cell death
What is an oncogene?
any gene in a healthy cell capable of promoting tumor growth
What is the genetic basis of cancer?
some cancers can result of mutation or deletion of a single potent tumor suppressor (retinoblastoma)
2-hit Hypothesis
- assumption that hereditary retinoblastoma has a single deletion of the RB1 tumor suppressor
- heterozygous mutations can increase susceptibility to cancers
What kind of genes are BRCA 1/2?
tumor suppressors
BRCA mutations in breast cancer increase susceptibility to what type of inhibitors?
PARP inhibitors (synthetic lethality)
PARP inhibitors
- trap PARP to DNA, unable to uncouple from DNA
- olaparib, rucaparib, niraparib
What happens during G0/G1?
- cell is quiescent or accumulating building blocks required for division
- cellular contents are duplicated
What happens during S phase?
- each of the 46 chromosomes is duplicated by the cell
What happens during the G2 phase?
- the cell “double checks” the duplicated chromosomes for error, making any needed repairs
What determines when the cells move from one phase of the cell cycle to the next?
cell cycle clock driven by cyclins paired with cyclin-dependent kinases
Non-cell specific agents
DNA damaging agents
- alkylators
- intercalaters
G1-specific agents
Mitogenic signaling
- kinase inhibitors
- hormone inhibitors
S-specific agents
DNA replication
- anti-metabolites
- anti-folates
- Topo I inhibitors
G2-specific agents
Sister Chromatid Separation
- Topo II inhibitors
M-specific agents
Chromosome Segregation
- microtubule inhibitors
Common Oncogenes
- KRAS
- PI3K
Common Tumor Suppressors
- TP53, p16, RB1
Palbociclib Target
CDK4/6 (approved for BRACA 1/2)
Palbociclib Class of Drug
Kinase Inhibitor
Palbociclib Cell Cycle Target
G1
Palbociclib Dose Limiting Side Effects
- neutropenia
- N/V/D
- fatigue
- similar to traditional chemotherapies
Drugs that are more effective against cycling cells at many phases of the cell cycle are called what?
- cell cycle non-specific
- alkylating agents and DNA intercalation agents
Limitation of cell kill in phase specific drugs
- higher drug doses may not result in greater tumor cell killing
Increased cell kills requires what?
- prolonged exposure
- one way to increase the number of cells present in the sensitive phase is to maintain therapeutic levels of a drug over a long period of time
Dose limiting toxicities of cancer chemotherapies?
Hematopoietic
- Infections
- hemostasis
- anemia
GI
- N/V
- Loss of appetite
Designing Chemotherapy Regimens
- combination of drugs with different mechanisms of action
- no additive toxicity for drugs with non-overlapping toxicity
- increased cell killing
What is the CHOP regimen
- Cyclophosphamide (alkylating agent)
- Doxorubicin (anthracycline)
- Vincristine (microtubule inhibitor)
- Prednisone (steroid)
What are the causes altered drug metabolism?
- increased transport of drugs out of the cell through efflux pumps (PgP, MRP)
- reduced transport into the cell (loss of drug importer, decreased membrane permeability)
- Decreased activation of prodrug
- Increased detoxification of drug molecule
What causes changes in drug target or function?
- increased expression of drug target through gene amplification (upregulation makes it harder to inhibit)
- emergence of mutant, structurally altered taraget
- emergence of cells bearing alterations in genes whose products are functionally redundant with the drug target
What causes physiological changes that promote resistance?
- metastasis
- massive stromalization
- changes in cell state such as EMT
What causes cell survival mechanisms?
- activation of anti-apoptoic regulators
- increased repair of damage caused by chemotherapies
What is the most common reason for resistance to multiple chemos at once?
drug transport out of cell
What are the two major strategies to endocrine therapy?
- stop steroid receptor function
- decrease production of steroids
Tamoxifen MOA
- selective estrogen receptor modulator
- blocks estrogen-dependent breast cancer cell proliferation
- estrogen agonist effects
- acts as antagonist and agonists
SERM (Tamoxifen) Receptor Target
ER/PR +
SERM (Tamoxifen) Side Effects
- hot flashes due to anti-estrogen effects
- incidence of cancer increased 3-fold
SERM (Tamoxifen) Pre or Post menopausal?
- pre and post menopausal
Tamoxifen Drug Interaction
Less effective in patients with a common CYP2D6 varient
Tamoxifen vs Raloxifene
Tamoxifen
- antiproliferative to Breast
- blocks bone resporption
- endometrial hyperplasia
Raloxifene
- no endometrial hyperplasia
- increases bone mass in osteoporosis
Selective Estrogen Receptor Down Modulator (Fluvestrant and Elacestrant) MOA
- Fluvestrant has pure ER antagonist that has no agonist effects
- Elacestrant acts as partial agonist at low doses and full SERD at high dose
SERD (Fluvestrant/Elacestrant) Receptor Target
ER
SERD Indication (Fluvestrant/Elacestrant)
- ER+ metastatic breast cancer in postmenopausal women who have progressed on other anti-estrogen therapy
What does Aromatase convert?
- Androstenedione to estrone
- testosterone to estradiol
What do aromatase inhibitors block?
- synthesis of estrogens
- not the synthesis of androgens or progestrone
Non-steroidal aromatase inhibitors MOA
- Letrozole and Anastrozole
- potent and selective competitive inhibitor of aromatase activity
Indication of Non-steroidal aromatase inhibitors
- treatment of breast cancer in postmenopausal women
- first line or when started after 3-5 years of tamoxifen
Steroidal Aromatase inhibitor MOA
- acts as false substrate that aromatase converts to reactive intermediate
- binds irreversibly at active site and inactivates enzyme
Indication of Steroidal Aromatase Inhibitor
ER+ breast cancer in postmenopausal women who have progressed on anti-estrogen therapy
Which anti-estrogen compound directly inhibits the activity of the estrogen receptor throughout the body?
Fulvestrant (directly binds to ER)
Chronic administration of GnRH analogs ____ pituitary GnRH receptors and leads to pituitary _____
down regulates, desensitization
GnRH Analogs MOA
- acute admin induces surge of LH and FSH (agonist effect)
- chronic administration downregulates pituitary GnRH and decreases synthesis of estrogen
Toxicity of GnRH analogs
- transient worsening of symptoms related to initial agonists
- long term side effects include hot flashes, sexual dysfunction, gynecomastia
Indication of GnRH analogs in breast cancer
- premenopausal breast cancer
Medications for postmenopausal women with ER+ disease
- tamoxifen
- Nonsteroidal aromatase inhibitors
- steroidal aromatase inhibitor (exemestane)
- pure anti-estrogens (fulvestrant)
Medications for premenopausal breast cancer
- GnRH agonists
- Surgical oophorectomy
- Tamoxifen
Important enzyme in steroid hormone biosynthesis for prostate cancer
Type II 5-alpha reductase
- testosterone –> DHT in prostate cells
17 alpha-hydrolyse and C17,20 lyase
- conversion of pregnenolone and progesterone to DHEA and androstenedione
Importance of DHT in prostate cancer
- DHT binds to androgen receptor (AR) in prostate cells
- binding of AR to DHT leads to translocation to the nucleus and action of genes that drive cell
Degareliz/Relugolix versus Leuprolide/Goselerin
- Degarelix/relugolix will not cuase flare of testosterone production
- long term side effects are the same
Abiraterone MOA
- inhibits the function of 17-alpha hydroylase and C17,20 lyase
- inhibits the conversion of pregnenolone and progesterone to DHEA and androstenedion
Abiraterone side effect
- increased levels of cholesterol
AR Receptor Antagonists
- enzalutamide
- apalutamide
- darolutamide
AR Receptor Antagonist MOA
- bind to AR to prevent AR translocation to the nucleus
AR Receptor Antagonist Target
androgen receptor
AR Indication
- metastatic and non metastatic prostate cancer
What is unique about the action of Tamoxifen vs Fluvestrant?
- it activates ER in the bone
Which compounds act directly on AR?
AR antagonists (enzalutamide)
What is cell signaling largely driven by?
the transfer of phosphate by a kinase to a target protein
What are the common targets of several kinases?
- serine
- tyrosine
- threonine
What balances the activity of kinases by removing phosphates?
Phosphatases
Type I Kinase inhibitors
bind to the active conformation of the kinase
Type II kinase inhibitor
bind and stabilize the inactive conformation of the kinase
Type III kinase inhibitor
occupy the allosteric pocket outside of the ATP binding pocket
Competitive kinase inhibitors
bind kinase in a reversible fashion and must compete with ATP for binding
Covalent kinase inhibitors
covalently bind with reactive nucleophilic cysteine residue proximal to the ATP-binding site, resulting in the blockage of the ATP site and irreversible inhibition
Gefitinib Target
EGFR
Gefitinib MOA
- Type I TKI
- competitively inhibits the enzyme by binding to the ATP binding site in the kinase domain
- inhibition of kinase activity turns off signal to proliferate
Gefitinib Indication
- patients with metastatic NSCLC whose tumors have EGFR exon 19 or exon 21 (L8585R) mutations
Gefitinib Toxicities
- fatigue
- rash
- diarrhea
Afatinib Target
All ErbB receptors (EGFR)
Afatinib MOA
- covalent kinase inhibitor inhibitor
Common toxicities for drugs targeting EGFR
EGFR inhibitor associated rash
Common resistance mutation to Gefitinib
T790M
Osimertinib MOA
covalent third generation EGFR inhbitor
Osimertinib indication
- effective against T790M mutant EGFR
What two genes are genomically amplified in breast cancer?
HER2 and EGFR
Lapatinib MOA
- reversible inhibitor of EGFR and HER2
Lapatinib targets
EGFR and HER2
Side Effects of Lapatinib
- N/V/D
- decompensated heart failure
Tucatinib MOA
- TKI that preferentially binds to HER2
Tucatinib Target
HER2
FLT3 mutations
- cytokine receptor important for hematopoietic cell survival and proliferation
- mutations lead to increased proliferation and decreased apoptosis
- acute myloid leukemia
First generation FLT3 inhibitor
- midostaurin (broad kinase inhibitor)
- type I
Second generation FLT3 inhibitor
- crenolanib (more specific than first generation midostaurin)
- type I
Type II FLT3 inhibitors
Quizartinib (specifc for ITD mutations)
What target is not driven by molecular diagnosticcs
- VEGFR (tumor angiogenesis)
- limited impact on disease
Imatinib MOA
Type II small molecule inhibitor of the Abl tyrosine kinase to decreased proliferation and enhance apoptotic cell death in CML and GIST
Imatinib Toxicities
- n/v
- fluid retention and edema
- neutropenia and thrombocytopenia
Treatment length for imatinib
life long
Ponatinib MOA
- BCR-Abl inhibitor
- effective against all the major mutant forms of BCR-Abl
Indication for Ponatinib
- inhibits the gatekeeper mutation of T315I that is resistant to all other BCR-Abl compounds
Major drivers of Lung Cancer
- Unknown
- EGFR
- KRAS
- EML4-ALK
EML4-ALK translocation
- When ALK becomes inappropriately fused to ELM4 it becomes cytoplasmic and constitutively active
Alectinib MOA
tyrosine kinase inhibitor of ALK
Dabrafenib MOA
second generation BRAF-V600 inhibitor
Indication of Dabrafenib
- combination with trametinib for treatment of BRAF V600E/K mutant metastatic melanoma
Trametinib MOA
- inhibts the kinase activity of MEK1 and MEK2
- Type III allosteric inhibitor
Trametinib adverse reactiosn
- rash
- diarrhea
- lymphedema
Limitation of Trametinib use
- not indicated for the treatment of patients who have received prior BRAF inhibitor therapy
Bruton’s Tyrosine Kinase
- important for normal B cell activity and B cell tumor growth
What type of kinase inhibitor is Ibrutinib?
Covalent
BTK inhibitors
Ibrutinib
Acalabrutinib
Acalabrutinib MOA
- second generation covalent BTK inhibitor
- also targets Cys481
- more potent and selective than ibrutinib
What type of kinase inhibitor is acalabrutinib
covaleng
Rapamycin Analogues
- sirolimus
- everolimus
What do rapamycin analogues target
mTOR (serine-threonine kinase)
Everolimus target
only mTORC1, not mTORC2
Oncotype Dx
helps to predict recurrence and therefore can prevent overtreatment, do not drive indications for specific therapies
What is the most dose-limiting toxicity of antimetabolites?
Myelosuppression
What target DNA and RNA precursors
anti-metabolites target the synthesis of essential molecules in proliferating cells
Purines
guanine, adenine
Pyridines
thymine, cytosine
MOA of pyrimidine analogs
- interfere with pyrimidine nucleotide synthesis (5-FU, capecitabine)
- Inhibition of DNA polymerase (Ara-C, Gemcitabine)
Uridine analogs
- primarily inhibit thymidine synthesis from uracil
5-FU MOA
- 5-FU is converted to FdUMP, which is an anlog of dUMP
- FdUMP forms ternary complex with thymidylate synthase and tetrahydrofolate
- this reaction cannot go to completion and thymidylate synthase is trapped
- TMP cannot be produced
- 5-FU also is converted into 5-UTP, which is incorporated into RNA and cannot be processed, affecting RNA stability
5-FU resistance
- downregulation of activating enzymes that convert 5-FU to FdUMP
- upregulating thymidylate synthase
5-FU susceptibility
~ 5% of the population has gene polymorphisms that result in deficiencyc of enzyme DPD which breaksdown 5-FU
- toxicity buildup
Drug Rescue For 5-FU
Thymidine
Drug Synergy of 5-FU
Leucovorate (increases the amount of covalent ternary complex with thymidylate synthase)
Capecitabine MOA
orally active prodrug of 5-FU
Cytosine Analogs MOA
primarily inhibit DNA synthesis
Cytarabine (Ara-C)
- Coverted to Ara-CTP intracellularly
- Ara-CTP is a competitive inhibitor of DNA polymerase alpha
- Cytidine deaminase converse cytarabine to non-toxic uracil arabinoside
- decreased levels of cytidine deaminase in the CNS makes Ara-C highly toxic in meningeal leukemia and lymphoma
Resistance mechanisms of cytarabine
- downregulation of activating enzymes
- upregulation of cytidine deaminase
- downregulation of transporter to move drug into cells
Gemcitabine vs Cytarabine
- increased cell permeability
- greater affinity for activating enzyme
- better evasion of DNA repair enzymes
- greater potency
Synergy Cytarabine
Tetrahydrouridine (cytidine deaminase inhibitor) to increase efficaccy and decrease resistance
Which drug is a nucleoside analog
Cytarabine
Purine analogs
6-MP
6-MP MOA
- inhibits multiple enzymes in the de novo purine biosynthesis pathway
- blocks synthesis of purine nucleotides
6-MP Metabolism
- TPMT polymophisms increase risk of toxicity
6-MP drug interactions
Xanthine oxidase inhibitors (allopurinol),
prevents the breakdown of 6-MP increasing toxicity
Which drug does allopurinol not block the breakdown of
6-TG
Importance of Folic Acid
- enters folate pool as dihydrofolate (FH2)
- reduction to tetrahydrofolate by DHFR
Inhibition of DHFR
- reduces tetrahydrofolate pools
- dihydrofolate (inactive folate) accumulates
Methotrexate MOA
mimics folic acid, bind and inhibit DHFR
Resistance to MTX
- amplification of DHFR gene or mutation of DHFR
- decreased polygultamation
Pemetrexed
- inhibitor of DHFR, thymidylate synthase, and glycinamide ribunucleotide formyltransferase
- decreased risk of drug resistance
Drug Rescue MTX
Leucovorin (increases intracellular pools of tetrahydrofolate and reverses toxic effects of DHFR inhibition)
What are alkylating agents?
drugs that generate reactive electrophilic (electron deficient) intermediates that react with nucleophilic (electron rich) groups on DNA and proteins
What is the most common site of alkylation
Guanine N7
Most effective anti-cancer drugs are what?
bifunctional akylating agents that produce DNA intra- and interstrand linkages
What part of the cell cycle do alkylating agents impact
not cell-cycle phase specific
What in cells can react with alkylating agents and “quench” their activity?
Glutathione
Side effects of alkylating agents
- mutagenic and carcinogenic (second malignancies/leukemias)
- normal cell populations rapidly proliferating (gut, bone marrow)
- N/V, myelosuppresion, carcinogenic and teratogenic
Chlorambucil
decrease nucelophilicity of nitrogen by adding aryl groups
Cyclophosphamide MOA
chemically stable prodrug that requires hydroxylation of hepatic ccytochrome P450
What byproduct does cyclophosphamide produce?
acrolein
Toxicities of cyclophosphamide
- mild bone marrow toxicity
- hemorrhagic cystitis
Treating bladder toxicities caused by cyclophosphamide
mesna
Mitomycin C (mutamycine)
- aziridine containing natural product
- funcctions as alkylating agent
- bifunctional adducts
- myelosuppression
Platinum drugs
- covalent crosslinkers, but not alkylating agents
- often intrastrand
Cisplatin MOA
aquo form is highly reacctive and a potent electrophile, reacts especially with thiols
Dose limiting toxicity of ccisplatin
nephrotoxicity (proximal tubule
other toxcities of cisplatin
- severe N/V
- minimal bone marrow toxicity
- peripheral neuropathy dose related
- ototoxicity
Drug resistancce of cisplatin
- increased intracellular concentration of non-protein thiols, especially glutathione
- increased expression of cellular GST
Mechanism of Action of Topoisomerase I Inhibitors
- bind to and form ternary drug-enzyme-DNA complex, blocks DNA religation
What phase of the cell cycle is most sensitive to Topo I
S phase
Drug resistance to Topo I Inhibitors
- Glutathione S-transferase overexpression (most important)
- PGP overexpression
- MRP overexpression
- topoisomerase downregulation or mutation to prevent inhibitor binding
Topo I Inhibitor Drugs
topotecan
irinotecan
Ininotecan Mutation
SN-38 polymorphisms that cause low expression of UGT1A1, causing increased toxicity of Irinotecan
Topo II Inhibitor MOA
inhibits Topo II to relieve torsional strain and untangles DNA
What type of compounds are Topo 2 Inhibitors
only ones that produce double stranded DNA breaks
Topo 2 Inhibitor Drugs
Anthracyclines (doxorubicin)
Etoposide
Topo 2 Inhibitor mechanisms of toxicity
- intercalators (AC)
- free radical causes DNA damage
- inhibition of Topo II presumed to be most important therapeutically
What causes the cardiotoxicity seen with anthracycliens
free radical damage
What part of the cell cycle do AC topo II inhibitors impact
non-cell cycle dependent
Toxicities of doxorubicin
- cardiotoxicity
- severe local tissue damage if extravasated
- read color
Which topo II AC has less cardiotoxicity?
epirubicin
Drug that mediates toxicity of anthracyclines
- Dexrazoxane
- protects against AC induced cardiotoxicity
Etoposide MOA
Topo 2 inhibitor that does not intercalate
What part of the cell cycle does etoposide topo 2 inhibitors impact
G2
Resistance to Topo II Inhibitors
- Glutathione S transferase overexpression (doxorubicin only)
- pgp overexpression
- MRP overexpression
- topo 2 downregulation or mutation
- increased DNA damage repair
What part of the cell cycle does bleomycin impact
G2 and M phases
What is a dose limiting toxicity of bleomycin
- pulmonary (myelosuppression is minimal)
- skin rash
- bleomycin is inactivated by bleomycin aminohydrolyase, which is in high concentrations everywhere but skin and lung
What is dynamic instability?
- shrinking and growing of microtubules
- polymerization (build)
-depolymerization (fall apart)
What is bleomycin
Topo 2 intercalator
Vinca alkaloids MOA
prevent microtubule assembly
Taxanes MOA
prevent microtubule disassembly
What drug requires a specific transporter to get into cells?
Vinca alkaloids (PGP)
Vinca Alkaloids dose limiting toxicity
peripheral neuropathy
(myelosuppression rare)
Eribulin vs vincristine
lower rate of neurotoxicity
Microtubule Stabilzers
Taxanes and epothilones
Taxanes MOA
blocks depolymerization and segregation of sister chromatids to daughter cells
Resistance of Taxanes
PGP
Dose limiting side effects of paclitaxel
- myelosuppression
- sensory neuropathy is reversible
Cabazitaxel vs Paclitaxel
- poor binding to PGP and MDR
- more efficacious in multi drug resistant tumors
Epothilones vs Taxanes
- not cross resistant with taxanes
- poor PGP substrate
Epothilones toxicity
- neurotoxicity like taxanes (reversible)
mAb nomenclature: o
mouse
mAb nomenclature: xi
chimeric
mAb nomenclature: zu
humanized
mAb nomenclature: u
fully human
Binding of several antibodies to a receptor on the surface of a cancer cell can lead to what?
CDC and antibody-dependent cellular toxicity (ADC)
Trastuzumab MOA
recombinant humanized monoclonal antibody specific for HER2
Trastuzumab Target
binds to HER2 receptor and induces recepter internalization and degredation
Trastuzumab Toxicities
- flu like symptoms
- cardiomyopathy
- risk of hypersensitivity reactions
Pertuzumab MOA
recombanized humanized monoclonal antibody specific for HER2
Pertuzumab Target
binds to HER2 and inhibitors dimerization (decreases signal)
Indication of Pertuzumab
used in combination with Trastuzumab
Cetuximab MOA
- competitively inhibits binding of EGF and TGF-alpha
- blocks phosphorylation and activation of receptor associated kinases
- leads to inhibition of cell growth and induction of apoptosis
Where does cetuximab and panitumumab bind to?
extracellular domain of the EGF receptor
Toxicities of Cetuximab
- severe infusion reactions in first dose
- acneiform rash
- asthenias
- fever
Bevacizumab MOA
- Binds to VEGF and blocks interaction with endothelial receptors
- blocks endothelial cell proliferation and new blood vessel formation
Is VEGF mutated in cancer?
no!, not an oncogene
Can bevacizumab be used as a monotherapy?
No, no evidence of efficacy as a single agnet
Bevacizumab vs Ramucirumab
- bevacizumab binds to the ligand
- ramucirumab binds to the receptor
What does rituximab target?
CD20 in B-cell non-hodgkin’s lymphoma
What does daratumumab target?
Cd38 in multiple myeloma
Trastuzumab Emtansine (T-DM1, Kadcyla) MOA
ADC consisting of cytotoxic agent emtansine linked to mAb trastuzumab
Adverse effects of trastuzumab emtansine
- AEs of trastuzumab
- thrombocytopenia
- hepatotoxicity
Trastuzumab/Derextecan MOA
ADC consisting of Topo I inhibitor and mAb
What is negative selection
strong affinity of immature T cell ans self MHC molecules that causes apoptosis
What is positive selection
binding is just right where T cells survive
Central tolerance
- all high avidity self reactive T cells have been
- need to empower T cells to kill cancers, which are often very different from self
Strategies to overcome central tolerance
- redirect T cells to cancer using genetic means
- redirect T cells to cancer using recombinant proteins
- lower the threshold to allow for targeting neo agents
BiTE target
CD3/CD19
BiTE drug
blinatumomab
Blinatumomab MOA
bind CD3 to physically bring an activated T cell in proximity with CD19
are BiTE drugs chimeric antibodies
NO
what do CTLA-4 and PD1 act as?
brakes or checkpoints on the immune system
Ipilimumab MOA
bind CTLA-4 receptor and reverses the CTL inhibition
What may be required with Ipilimumab?
high dose corticosteroids
Pembrolizumab MOA
bind PD-1 receptor blocks interaction with PDL-1 which is expressed on T cells
Sipulcel-T
PAP-GM-CSF to stimulate a patient’s own immune system to attack the cancer
Side effects Sipulcel-T
flu like symptoms
possible increased risk of stroke
CAR-T cell target
CD19
