Yang Post-MT (Immunology, CAR-T, Immune Checkpoint Inhibitors, Personalized BC Therapies) Flashcards
5What is the most prominent granulocyte (by percentage)? Least prominent?
Most: Neutrophils (70%)
Least: Eosinophils (5%)
What are the cells of Innate Immunity?
NK Cells (cytotoxic)
DCs (APCs)
Mast Cells (inflammation)
Macrophages (phagocyte)
Neutrophils
Basophils
Eosinophils
What is the primary Antigen-Presenting Cell of the immune system?
Dendritic Cells
CD4+ T Cells are also known as ______ cells, whereas CD8+ T Cells are also known as _____ cells.
CD4+ = T Helper Cells
CD8+ = Cytotoxic T Cells
MHC Class I molecules present self & foreign antigens to what type of T Cell?
Cytotoxic T Cells
MHC Class II molecules present foreign antigens to what type of T Cell?
T Helper Cells
What HLA letters are MHC Class I? MHC Class II?
Class I: A, B, C
Class II: The “Ds”…
DP, DM, DOA, DOB, DQ, DR
In what MHC Class (I or II) is the peptide binding groove bigger?
Class II (much bigger)
Which of the two immunity forms (Cell-Mediated or Humoral) involves mediation via secreted ABs?
Humoral
CD4+ T Cells secrete _____, which serve to stimulate B Cell differentiation into Plasma Cells.
cytokines
T Cells originate within _______, & mature within the ______.
bone marrow ; thymus
The Primary Activation Signal of Cytotoxic T Cells involves TCR / MHC Class I association… What is the Secondary Activation Signal?
CD28 (from Cytotoxic T Cell) + CD80 / 86 association (from APC).
How do Tregs promote cancer development / progression?
Inhibition of anticancer immunity within tumor microenvironment.
What surface interaction at the level of the T & B Cell triggers B Cells to make more copies of itself (ie. Proliferation Signal)?
CD40 (from B Cell) / CD40L (from T Cell) associations
Which of the following IS NOT a class of immunoglobulin?
IgA
IgB
IgD
IgE
IgG
IgM
IgB
Of the five AB subtypes (ADEGM), which one becomes dimeric in the GIT / Respiratory Tract?
IgA
Of the five AB subtypes (ADEGM), which one provides immunity against Helminth Infections?
IgE
What is the main type of AB?
IgG (75%)
Of the four subclasses of IgG ABs (G1, G2, G3, G4), which ones can cross the Placenta?
G1, G3, G4
What AB subclass is the largest?
IgM
Which AB (ADEGM) is first produced in the humoral immunity response)
IgM
ITAMs (Immunoreceptor Tyrosine-Based Activation Motif) work intracellularly by binding to _____, which initiates T Cell activation.
ZAP70
What molecules do activated Cytotoxic T Cells release to kill pathogenic invaders?
Perforins (perforate cell membranes)
Granzymes (apoptosis trigger)
Granulysin (form pores in microbe cell walls)
What is the underlying premise of CAR-T Cell therapies?
Collect T Cells, add CAR gene that targets specific cancer antigen, grow in the lab, re-infuse back into patient.
We have five generations of existing CAR-T Cell therapies… Which generation is the only one approved for use?
2nd Gen
What component of the CAR cell binds to cancer antigens?
scFv (Single Chain Variable Fragment)
What motif of the CAR Cell binds ZAP70 & activates TCR signaling pathways?
CD3 Zeta
What are the three components of the CAR-T Cell?
1) scFv
2) Hinge
3) CD3 Zeta
How many co-stimulators do 2nd Gen CAR-T Cells contain? 3rd Gen?
2nd Gen: One Co-Stim
3rd Gen: Two Co-Stim
What B Lymphocyte Antigen serves as a biomarker for Lymphomas & Leukemias?
CD19
What B Lymphocyte Antigen serves as a biomarker for Multiple Myelomas?
BCMA (B Cell Maturation Antigen)
Name of drug that targets CD19 antigen in particular Lymphomas / Leukemias?
Kymriah
Which two CAR-T therapies target BCMAs in Multiple Myelomas?
Carvykti / Abecma
What are the two inhibitory checkpoint molecules we discussed in class?
CTLA-4, PD-1
What are the two FDA approved drugs that target CTLA-4?
Ipilimumab, Tremelimumab
What are the three FDA approved drugs that target PD-1?
Nivolumab, Pembrolizumab, Cemiplimab
Atezolizumab, Avelumab, & Durvalumab are all FDA approved drugs that bind to what target?
PD-L1
Certain PD-1 drugs such as Cemiplimab are limited against ____ tumors, which contain dense outer coatings that prevent drug penetrance.
cold
Which PD-L1 drug can be used for Metastatic, Triple Negative Breast Cancers (ie. Worst Case)?
Atezolizumab
What drug is used in combination with Nivolumab in treating Melanoma tumors, as it binds LAG-3 & prevents inhibitory LAG-3 / FGL1 associations?
Relatlimab
Targeted Therapies are typically introduced to Stage IV BC regimens after how many rounds of chemotherapy?
2 - 3 Rounds
Is a HER2+ prognosis better or worse relative to Luminal A / B?
Worse
Worst prognosis breast cancer?
ER-, PR-, HER2- (Triple Negative)
What is the major downstream signaling pathway that gets activated upon HER1 / HER2 dimerization?
PI3K Pathway
Metastatic / Recurrent HER2+ Breast Cancer therapies often see Trastuzumab & Pertuzumab being combined with what drug?
Docetaxel (anti-mitotic drug)
Which MAB therapy is reserved for Trastuzumab / Pertuzumab failure?
Margetuximab
In what stage of breast cancer would it be most appropriate to use T-DM1: Early (ie. Post-Surgery) or Late-Staged (when metastasis has occurred)?
Early (as goal is to kill & Emtansine is cytotoxic, not to reduce further spreading)
Which drug would I combine with Lapatinib to treat HER2 overexpressing breast cancers: Capecitabine or Letrozole?
Letrozole… Is an Aromatase Inhibitor specifically for HER2 overexpressing breast cancers!
Which TKI drug demonstrates extensive HER2 Receptor selectivity?
Tucatinib
How does Palbociclib work?
Blocks Rb phosphorylation, which prevents cell from passing R point in cell cycle & arrests it in G1 Phase.
Everolimus binds what substrate?
mTORC1
Alpelisib binds what substrate?
Alpha-Specific PI3K
Olaparib & Talazoparib are indicated for ____-mutated, HER2- breast cancers.
BRCA
Sacituzumab Govitecan conjugate is indicated for what type of breast cancer?
Triple Negative Breast Cancers (& received at least two prior therapies for Metastatic Disease).
