Biologic Antineoplastics - Fitz

Question 1

What is the MOA of Bortezomib?

Answer 1

• Target altered processes: Inhibit 26S proteosome in B-cells
  
  • increase ubiquitin → apoptosis

Question 2

What drug class is Bortezomib (BOR) in?

Answer 2

• Monoclonal antibody (MAB)
• Antineoplastic
• Cell cycle non-specific

***Unlike any other antineoplastic drugs we have studied so far.

Question 3

What is the MOA of Lenalidomide/Thalidomide?

Answer 3

• Prevent angiogenesis
  
  • selectively inhibits secretion of proinflammatory cytokines (e.g. antiTNF-alpha)
  • Decreases VEGF
  • enhances cell-mediated immunity by stimulating proliferation of anti-CD3 stimulated T-cells (T_H2, T_H1)
  • inhibits trophic signals to angiogenic factors in cells

Question 4

What drug class is Lenalidomide/Thalidomide in?

Answer 4

• Antineoplastic
• Angiogenesis Inhibitor
• Cell cycle non-specific

***Unlike any other antineoplastic drugs we have studied so far.

Question 5

What is the MOA of Interleukin 2?

Answer 5

• Immune system stimulant: CYTOKINE
  
  • hematopoietic supporting agent
  • stimulates proliferation of CD4+ T-cells and NK cells

Question 6

What drug class is Interleukin 2 in?

Answer 6

• Immunologic agent
• Immune system modulator
• Cell cycle non-specific

***Opposite of immunosuppressives like Dexamethasone & Prednisone.

Question 7

What is the MOA of Prednisone?

Answer 7

• Immune system modulator: Glucocorticoid
  
  • glucocorticoid receptor agonist
  • block Phospholipase 2 & COX
    
    • prevents inflammation by blocking the production of both leukotrienes and prostaglandins

Question 8

What drug class is Prednisone in?

Answer 8

• Immunosuppressives
• Glucocorticoids
• Similar to Dexamethasone
• Opposite of Interleukin 2

Question 9

What is the MOA of Melphalan?

Answer 9

• Alkylating agent → crosslinks DNA

Question 10

What drug class is Melphalan in?

Answer 10

• Antineoplastics
• Cell cycle non-specific
• Disrupt DNA, prevent DNA repair and/or interfere with RNA synthesis
  
  • similar to Cisplatin, Doxorubicin, Etoposide
• Alkylating agent
  
  • similar to Busfulfan, Carmustine, Cyclophosphamide, Temozolamide

Question 11

What is the MOA of 6-Mercaptopurine?

Answer 11

• Prevent DNA synthesis by blocking purine synthesis
  
  • “pseudofeedback” of PNP (purine nucleoside phosphorylase) and PRPP (phosphoribosyl pyrophosphate)
    
    • PNP = 1st step in purine synthesis
    • PRPP = 1st committed step in purine synthesis

Question 12

What drug class is 6-Mercaptopurine in?

Answer 12

• Antineoplastic
• Cell cycle specific: S-phase
• Prevent DNA synthesis
  
  • similar to Methotrexate, 5-Fluorouracil, Ara-C, Fludarabine

Question 13

What is the difference between Lymphokine-activated killer cells (LAK) and Cytokine-induced killer cells (CIK)?

Answer 13

• Lymphokine-activated killer cell (LAK)
  
  • NK cell that has been stimulated to kill tumor cells
• Cytokine-induced killer cell (CIK)
  
  • CD8+ cell that has been stimulated to kill tumor cells

Question 14

How are Lymphokine-activated killer cells produced compared to Cytokine-induced killer cells?

Answer 14

• LAK cell production:
  
  • NK cells are cultured in the presence of Interleukin 2, results in the development of effector cells which are cytotoxic to tumor cells
• CIK cell production:
  
  • ​CD8⁺ T-cells are cultured in the presence of interferon-gamma (IFN-γ), anti-CD3 antibody , recombinant human interleukin (IL-) 1 and recombinant human interleukin (IL)-2

Question 15

What is a potential mechanism whereby treatment with CIK cells could have produced the improvement in skin lesions reported in the Lin et. al. case study?

Answer 15

• Skin lesions caused by cancer
  
  • CIK cell therapy kills cancer → killing source of problem makes skin lesions better
• Skin lesions caused by immune system
  
  • immune system response due to presence of cancer → CIK cell therapy kills cancer