Yang Post-MT (Immunology, CAR-T, Immune Checkpoint Inhibitors, Personalized BC Therapies)

Question 1

5What is the most prominent granulocyte (by percentage)? Least prominent?

Answer 1

Most: Neutrophils (70%)
Least: Eosinophils (5%)

Question 2

What are the cells of Innate Immunity?

Answer 2

NK Cells (cytotoxic)
DCs (APCs)
Mast Cells (inflammation)
Macrophages (phagocyte)
Neutrophils
Basophils
Eosinophils

Question 3

What is the primary Antigen-Presenting Cell of the immune system?

Answer 3

Dendritic Cells

Question 4

CD4+ T Cells are also known as ______ cells, whereas CD8+ T Cells are also known as _____ cells.

Answer 4

CD4+ = T Helper Cells
CD8+ = Cytotoxic T Cells

Question 5

MHC Class I molecules present self & foreign antigens to what type of T Cell?

Answer 5

Cytotoxic T Cells

Question 6

MHC Class II molecules present foreign antigens to what type of T Cell?

Answer 6

T Helper Cells

Question 7

What HLA letters are MHC Class I? MHC Class II?

Answer 7

Class I: A, B, C

Class II: The “Ds”…
DP, DM, DOA, DOB, DQ, DR

Question 8

In what MHC Class (I or II) is the peptide binding groove bigger?

Answer 8

Class II (much bigger)

Question 9

Which of the two immunity forms (Cell-Mediated or Humoral) involves mediation via secreted ABs?

Answer 9

Humoral

Question 10

CD4+ T Cells secrete _____, which serve to stimulate B Cell differentiation into Plasma Cells.

Answer 10

cytokines

Question 11

T Cells originate within _______, & mature within the ______.

Answer 11

bone marrow ; thymus

Question 12

The Primary Activation Signal of Cytotoxic T Cells involves TCR / MHC Class I association… What is the Secondary Activation Signal?

Answer 12

CD28 (from Cytotoxic T Cell) + CD80 / 86 association (from APC).

Question 13

How do Tregs promote cancer development / progression?

Answer 13

Inhibition of anticancer immunity within tumor microenvironment.

Question 14

What surface interaction at the level of the T & B Cell triggers B Cells to make more copies of itself (ie. Proliferation Signal)?

Answer 14

CD40 (from B Cell) / CD40L (from T Cell) associations

Question 15

Which of the following IS NOT a class of immunoglobulin?

IgA
IgB
IgD
IgE
IgG
IgM

Answer 15

IgB

Question 16

Of the five AB subtypes (ADEGM), which one becomes dimeric in the GIT / Respiratory Tract?

Answer 16

IgA

Question 17

Of the five AB subtypes (ADEGM), which one provides immunity against Helminth Infections?

Answer 17

IgE

Question 18

What is the main type of AB?

Answer 18

IgG (75%)

Question 19

Of the four subclasses of IgG ABs (G1, G2, G3, G4), which ones can cross the Placenta?

Answer 19

G1, G3, G4

Question 20

What AB subclass is the largest?

Answer 20

IgM

Question 21

Which AB (ADEGM) is first produced in the humoral immunity response)

Answer 21

IgM

Question 22

ITAMs (Immunoreceptor Tyrosine-Based Activation Motif) work intracellularly by binding to _____, which initiates T Cell activation.

Answer 22

ZAP70

Question 23

What molecules do activated Cytotoxic T Cells release to kill pathogenic invaders?

Answer 23

Perforins (perforate cell membranes)

Granzymes (apoptosis trigger)

Granulysin (form pores in microbe cell walls)

Question 24

What is the underlying premise of CAR-T Cell therapies?

Answer 24

Collect T Cells, add CAR gene that targets specific cancer antigen, grow in the lab, re-infuse back into patient.

Question 25

We have five generations of existing CAR-T Cell therapies... Which generation is the only one approved for use?

Answer 25

2nd Gen

Question 26

What component of the CAR cell binds to cancer antigens?

Answer 26

scFv (Single Chain Variable Fragment)

Question 27

What motif of the CAR Cell binds ZAP70 & activates TCR signaling pathways?

Answer 27

CD3 Zeta

Question 28

What are the three components of the CAR-T Cell?

Answer 28

1) scFv 2) Hinge 3) CD3 Zeta

Question 29

How many co-stimulators do 2nd Gen CAR-T Cells contain? 3rd Gen?

Answer 29

2nd Gen: One Co-Stim 3rd Gen: Two Co-Stim

Question 30

What B Lymphocyte Antigen serves as a biomarker for Lymphomas & Leukemias?

Answer 30

CD19

Question 31

What B Lymphocyte Antigen serves as a biomarker for Multiple Myelomas?

Answer 31

BCMA (B Cell Maturation Antigen)

Question 32

Name of drug that targets CD19 antigen in particular Lymphomas / Leukemias?

Answer 32

Kymriah

Question 33

Which two CAR-T therapies target BCMAs in Multiple Myelomas?

Answer 33

Carvykti / Abecma

Question 34

What are the two inhibitory checkpoint molecules we discussed in class?

Answer 34

CTLA-4, PD-1

Question 35

What are the two FDA approved drugs that target CTLA-4?

Answer 35

Ipilimumab, Tremelimumab

Question 36

What are the three FDA approved drugs that target PD-1?

Answer 36

Nivolumab, Pembrolizumab, Cemiplimab

Question 37

Atezolizumab, Avelumab, & Durvalumab are all FDA approved drugs that bind to what target?

Answer 37

PD-L1

Question 38

Certain PD-1 drugs such as Cemiplimab are limited against ____ tumors, which contain dense outer coatings that prevent drug penetrance.

Answer 38

cold

Question 39

Which PD-L1 drug can be used for Metastatic, Triple Negative Breast Cancers (ie. Worst Case)?

Answer 39

Atezolizumab

Question 40

What drug is used in combination with Nivolumab in treating Melanoma tumors, as it binds LAG-3 & prevents inhibitory LAG-3 / FGL1 associations?

Answer 40

Relatlimab

Question 41

Targeted Therapies are typically introduced to Stage IV BC regimens after how many rounds of chemotherapy?

Answer 41

2 - 3 Rounds

Question 42

Is a HER2+ prognosis better or worse relative to Luminal A / B?

Answer 42

Worse

Question 43

Worst prognosis breast cancer?

Answer 43

ER-, PR-, HER2- (Triple Negative)

Question 44

What is the major downstream signaling pathway that gets activated upon HER1 / HER2 dimerization?

Answer 44

PI3K Pathway

Question 45

Metastatic / Recurrent HER2+ Breast Cancer therapies often see Trastuzumab & Pertuzumab being combined with what drug?

Answer 45

Docetaxel (anti-mitotic drug)

Question 46

Which MAB therapy is reserved for Trastuzumab / Pertuzumab failure?

Answer 46

Margetuximab

Question 47

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)?

Answer 47

Early (as goal is to kill & Emtansine is cytotoxic, not to reduce further spreading)

Question 48

Which drug would I combine with Lapatinib to treat HER2 overexpressing breast cancers: Capecitabine or Letrozole?

Answer 48

Letrozole... Is an Aromatase Inhibitor specifically for HER2 overexpressing breast cancers!

Question 49

Which TKI drug demonstrates extensive HER2 Receptor selectivity?

Answer 49

Tucatinib

Question 50

How does Palbociclib work?

Answer 50

Blocks Rb phosphorylation, which prevents cell from passing R point in cell cycle & arrests it in G1 Phase.

Question 51

Everolimus binds what substrate?

Answer 51

mTORC1

Question 52

Alpelisib binds what substrate?

Answer 52

Alpha-Specific PI3K

Question 53

Olaparib & Talazoparib are indicated for ____-mutated, HER2- breast cancers.

Answer 53

BRCA

Question 54

Sacituzumab Govitecan conjugate is indicated for what type of breast cancer?

Answer 54

Triple Negative Breast Cancers (& received at least two prior therapies for Metastatic Disease).