Immune Therapy-Oncology

Question 1

REVIEW: What drug is able to target HER2?

Answer 1

• Tucatinib

Question 2

REVIEW: What drugs targets a kinases that is produced by the formation of the Philadelphia chromosome?

Answer 2

• Imatinib

Question 3

REVIEW: What drugs is not a covalent kinase inhibitor?

Answer 3

• Gefitinib

Question 4

What was the first attempt to use immunotherapy?

Answer 4

• Coley’s Toxin: Basically bacteria that was injected into the tumor to start immune response

Question 5

Within the cells of the immune system, which one are the most important?

Answer 5

• T & B Cells [Adaptive Immunity]

Question 6

What are B Cells?

Answer 6

• Antibody producing cells
• B Cell is triggered by antigen and engulfs it, that makes antigen fragments to help attract the matching T Cell with makes the antibodies

Question 7

What are some of the common nomenclatures for monoclonal antibodies?

Answer 7

Stem:
- mab
Substem:
- Mouse: -o-
- Chirmeric: -xi-
- Humanized: -zu-
- Fully Human: -u-

Question 8

What does it mean when antibodies are two tiered?

Answer 8

• They are able to affect several cancer events
• Binding several antibodies to the cancer surface could lead to CDC, ADCC, and elimination of the Tumor cell

Question 9

What is CDC and ADCC in terms of cancer and oncolgy?

Answer 9

• CDC: Complement-dependent cytotoxicity
• ADCC: antibody-dependent cellular cytotoxicity

Question 10

What are the HER2 monoclonal antibodies that are used?

Answer 10

• Trastuzumab & Pertuzumab

Question 11

What is the mechanism of action for trastuzumab?

Answer 11

• bind to the HER2 receptor and induce cytotoxicity [calling over NK cells]
• Will also decrease HER2 on the surface with degradation

Question 12

What is the primary indication for Trastuzumab?

Answer 12

• Treatment of breast cancers with HER2 overexpression

Question 13

What are some of the toxicites that are for Trastuzumab?

Answer 13

• Flu-like symptoms, Cardiomyopathy [increased with Adriamycin], NO myelosuppression

Question 14

What is the important thing to know about Trastuzumab?

Answer 14

• Humanized monoclonal antibody for HER2
• Linked to Human IgG kappa?

Question 15

What is the mechanism of action for Pertuzumab?

Answer 15

• Binds to HER2 to inhibit dimerization [dimerization is important for HER2 reponses]

Question 16

What is the important thing to know about Pertuzumab?

Answer 16

• Humanized monoclonal antibody for HER2

Question 17

What is the CLEOPATRA trial?

Answer 17

• It showed that Pertuzumab+Trastuzuamb was great
• NO differences in safety and increased survival

Question 18

What was some ways that Fc engineering improved therapeutic antibodies?

Answer 18

• Margetuximab: increase in CD16A [NK Cells] & decrease in DC32B [B cells]

Question 19

What are the EGFR monoclonal antibodies that are using cancer?

Answer 19

• Cetuximab & Panitumumab

Question 20

What is the mechanism of action for Cetuximab?

Answer 20

• Binds to extra cellular EGFR that inhibits EGR & TGF leading to inhibition of Cell Growth and induce apoptosis

Question 21

What is the primary indication for Cetuximab?

Answer 21

• Treatment for colorectal, head, and neck

Question 22

What is important to know about Cetuximab?

Answer 22

• Chimeric antibody

Question 23

What are some of the toxicities for Cetuximab?

Answer 23

• infusion reactions [1st dose]
• Rash
• Muscle weakness
• Fever

Question 24

What is the mechanism of action for Panitumumab?

Answer 24

• Binds to the EGFR and inhibits the binding of EGF and TGF that leads to inhibition of cell growth and induce apoptosis

Question 25

What are the side effects of Panitumumab?

Answer 25

- Skin rash - Diarrhea

Question 26

What is important to know about Panitumumab?

Answer 26

- Fully humanized monoclonal anitbody

Question 27

What is the mechanism of action for Bevacizumab?

Answer 27

- **Binds to VEGF that blocks the intercalation** with endothelial receptor **stoping cell proliferation**

Question 28

What is important to know for Bevacizumab?

Answer 28

- NOT good as single agent [combom with 5-FU] - Humanized monoclonal antibody

Question 29

Which one of the following antibodies targets HER2? A] Neratinib B] Cetuximab C] Lapatinib D] Pertuzumab

Answer 29

- Pertuzumab

Question 30

What was the first immunotherapy?

Answer 30

- Coley Toxin

Question 31

What type of antibody is fakeumab?

Answer 31

- Fully Human

Question 32

What are the important B cell markers?

Answer 32

- CD20: affects the middle - CD19: whole thing - CD38: Early - Mid - End

Question 33

How does CD20 work within B-Cell Receptors?

Answer 33

- Drives the **proliferation** [plays a role in lymphoma] - Antibodies binding to CD20 can inhibit cell prliferation AND induce antibody-dependent cytotoxcity

Question 34

How does CD38 work in B Cells?

Answer 34

- CD38 are highly expressed **in plasma B cells that make antibodies** [eliiminate multiple myeloma by **ADCC and CDC**

Question 35

What is the mechanism of action for Trastuzumab-Emtansine [TDM1]?

Answer 35

- Binds to HER2 and enters the cell inhibiting microtubule assebly

Question 36

What is important to know about Tratuzumab-Emtansine?

Answer 36

- Has BOTH cytoxic agent [Emtansine] & monoclonal antibody [Tratuzumab]

Question 37

What are the toxicities of Trastuzumab-Emtansine?

Answer 37

- Adverse events of trastuzumab - Thrombocytopenia - Hepatotoxicity

Question 38

What is the way that T-cells are made?

Answer 38

- **Start in the bone marrow** that moves **to the thymus** to mature - T cell **combines with MHC** to become **active and kill the cell** - T cells decrease making memory

Question 39

What are some of the Bispecific T-cell Engagers [BiTE]?

Answer 39

- Blinatumomab, Mosunetuzumab,Teclistamab, Taquetamab

Question 40

What is the mechanism of action for Blinatumomab?

Answer 40

- Binds to **CD3 to bring an activated T-cell into range of CD19; which is highly expressed on B cell and Leukemia** [lyase tumor] - NOT chimeric

Question 41

What is the mechanism of action for Mosunetuzumab?

Answer 41

- Targets CD3 and CD20 on non-Hodgkins

Question 42

What is the mechanism of action for Teclistamab?

Answer 42

- Targets T cells and B cells on Myeloma cells

Question 43

What is the mechanism of action for Taquetamab?

Answer 43

- **Targets CD3 and Human GPRC5D** on Myelona cells

Question 44

What acts as "brakes" or "checkpoints" on the immue system?

Answer 44

- CTLA-4 and PD1

Question 45

What drugs affect CTLA-4 and PD1?

Answer 45

- Ipilimumab, Pembrolizumab, Atezolizumab

Question 46

What is the mechanism of action for Ipilimumab?

Answer 46

- Binds to **CTLA-4 and reverse the CTL inhibition** [CTL can destroy tumors] - Treatment for **metastatic melanoma**

Question 47

What are the side effects of Ipilimumab?

Answer 47

- GI issues - Dermatitis

Question 48

What is the mechanism of Pembrolizumab?

Answer 48

- Binds the PD-1 receptor and **blocks its interaction with PD-L1/2** leading to tumor killing

Question 49

What is important to know about pembrolizumab? | treatment?

Answer 49

- PD-1 = T cell - PD-L1 = Tumor Cells - Treatment for **Metastatic melanoma** [following Ipilimumab & BRAF] and **NSCLC** [PD-L1+]

Question 50

What is the mechanism of action for Atezolizumab?

Answer 50

- **Binds to PD-L1 and blocks the interaction with PD-1**