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PHAR 211 - Personalized Medicine > Yang Post-MT (Immunology, CAR-T, Immune Checkpoint Inhibitors, Personalized BC Therapies) > Flashcards

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

1
Q

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

A

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

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2
Q

What are the cells of Innate Immunity?

A

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

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3
Q

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

A

Dendritic Cells

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4
Q

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

A

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

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5
Q

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

A

Cytotoxic T Cells

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6
Q

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

A

T Helper Cells

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7
Q

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

A

Class I: A, B, C

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

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8
Q

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

A

Class II (much bigger)

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9
Q

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

A

Humoral

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10
Q

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

A

cytokines

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11
Q

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

A

bone marrow ; thymus

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12
Q

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

A

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

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13
Q

How do Tregs promote cancer development / progression?

A

Inhibition of anticancer immunity within tumor microenvironment.

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14
Q

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

A

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

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15
Q

Which of the following IS NOT a class of immunoglobulin?

IgA
IgB
IgD
IgE
IgG
IgM

A

IgB

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16
Q

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

A

IgA

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17
Q

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

A

IgE

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18
Q

What is the main type of AB?

A

IgG (75%)

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19
Q

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

A

G1, G3, G4

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20
Q

What AB subclass is the largest?

A

IgM

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21
Q

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

A

IgM

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22
Q

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

A

ZAP70

23
Q

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

A

Perforins (perforate cell membranes)

Granzymes (apoptosis trigger)

Granulysin (form pores in microbe cell walls)

24
Q

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

A

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

25
Q

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

A

2nd Gen

26
Q

What component of the CAR cell binds to cancer antigens?

A

scFv (Single Chain Variable Fragment)

27
Q

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

A

CD3 Zeta

28
Q

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

A

1) scFv
2) Hinge
3) CD3 Zeta

29
Q

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

A

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

30
Q

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

A

CD19

31
Q

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

A

BCMA (B Cell Maturation Antigen)

32
Q

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

A

Kymriah

33
Q

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

A

Carvykti / Abecma

34
Q

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

A

CTLA-4, PD-1

35
Q

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

A

Ipilimumab, Tremelimumab

36
Q

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

A

Nivolumab, Pembrolizumab, Cemiplimab

37
Q

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

A

PD-L1

38
Q

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

A

cold

39
Q

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

A

Atezolizumab

40
Q

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

A

Relatlimab

41
Q

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

A

2 - 3 Rounds

42
Q

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

A

Worse

43
Q

Worst prognosis breast cancer?

A

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

44
Q

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

A

PI3K Pathway

45
Q

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

A

Docetaxel (anti-mitotic drug)

46
Q

Which MAB therapy is reserved for Trastuzumab / Pertuzumab failure?

A

Margetuximab

47
Q

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)?

A

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

48
Q

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

A

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

49
Q

Which TKI drug demonstrates extensive HER2 Receptor selectivity?

A

Tucatinib

50
Q

How does Palbociclib work?

A

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

51
Q

Everolimus binds what substrate?

A

mTORC1

52
Q

Alpelisib binds what substrate?

A

Alpha-Specific PI3K

53
Q

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

A

BRCA

54
Q

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

A

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

PHAR 211 - Personalized Medicine (12 decks)

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