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Chemotherapy BMSC2210 > Lecture 17 Therapeutic antibodies, biological therapies, new directions > Flashcards

Lecture 17 Therapeutic antibodies, biological therapies, new directions Flashcards

1
Q

What are the requirements for humanized antibody use?

A

Antigens need to be overexpressed in tumors

Antigens expressed need to be accessible to antibodies

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2
Q

How do humanized antibodies work?

A

Prevent interaction of growth factor with cell surface receptor or recruit components of the immune system to kill antibody-bound cancer cells
OR conjugation of a toxin/radioisotope to antibody
In most cases, the MOA is not known

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3
Q

What is a hybridoma cell line?

A

cell line originating from the combination of spleen and cancer cells

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4
Q

What is a single chain variable region fragments (scFv)?

A

A smaller version of humanized antibodies
Synthesized by bacteriophages
Advantageous as smaller and therefore able to penetrate the tissue more effectively

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5
Q

Explain Herceptin’s mechanism of action

A

Targets extracellular domain of HER2

Mechanism unclear

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6
Q

What is the clinical use of Herceptin?

A

Breast cancers that do not respond to estrogen or progesterone
Effective in metastatic breast cancer but less clear in early stage

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7
Q

What is the main adverse effect of Herceptin?

A

Heart failure

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8
Q

What new development is being tried with Herceptin?

A

linking emtansine (a tubulin inhibitor normally too toxic for cells) to Herceptin to kill HER2+ metastatic breast cancer cells

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9
Q

Explain the mechanism of action of Bevacizumab

A

Binds to vascular endothelial growth factor (VEGF)

Prevents angiogenesis

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10
Q

What is the clinical use of Bevacizumab?

A

Colorectal cancer - extends life expectancy

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11
Q

What are the adverse effects of Bevacizumab?

A

Hypertension

Intestinal bleeding

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12
Q

What is the mechanism of action of Rituximab?

A

Binds to CD20 which is expressed on all B cells in non-Hodgkins lymphoma

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13
Q

What is the clinical use of Rituximab?

A

Therapy for non-Hodgkins lymphoma and other lymphomas and leukemias

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14
Q

What are the side effects of Rituximab?

A

fever and hypotension

cardiac problems

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15
Q

What is the mechanism of action of Cetuximab?

A

Targets EGF receptor

May interfere with cancer cell growth by preventing EGF binding

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16
Q

What are the clinical uses of Cetuximab?

A

Colorectal cancer treatment

17
Q

What are the side effects of Cetuximab?

A

Fever

Hypotension

18
Q

What is the mechanism of action of L-Asparaginase

A

Inhibits asparaginase
Part of the pathway which converts exogenous asparagine into aspartate
Therefore aspartate is not formed and able to be used for protein synthesis/cell growth

19
Q

What are the clinical uses of L-asparagine?

A

childhood acute lymphocytic leukemia with vincristine and prednisone

20
Q

What are the 2 major types of interferons?

A 
Type I (IFN- alpha and beta)
Type II (IFN-gamma)
21
Q

What are the functions of IFNs?

A

Promote apoptosis in cancer cells

Stimulate immune cells to recognize and kill cancer cells

22
Q

What are the clinical uses of IFN-alpha2a and b?

A

AIDS-related Kaposi’s sarcomas
Hairy cell leukemia
Promising results in extending disease-free survival in melanoma

23
Q

In what form are interferon alphas given?

A

IM
SC
IV

24
Q

What are some of the associated side effects of interferon alpha?

A

high dose = depression and loss of energy

25
Q

What are the clinical uses of interleukin 2?

A

renal cell carcinoma

melanoma

26
Q

What are the side effects of interleukin 2?

A

Hypotension
Liver damage etc.
Note: they are all reversible

27
Q

What is the max no of doses in which tolerance is reached?

A

14

28
Q

What is the use of granulocyte-monocyte colony stimulating factor?

A

Used to reconstitute myeloid blood cells after stem cell and bone marrow transplantation
In cancer patients, may stimulate the cellular immune system

29
Q

Which cells does IL-12 stimulate?

A

B cells
T cells
NK cells

30
Q

Explain the racial variation that occurs in response to Iressa

A

Japanese 3x more likely to respond than Americans
May be due to particular mutations of the Iressa binding site on EGFR
Need for personalized medicine - done via large scale DNA sequence profiling of individuals and populations

Chemotherapy BMSC2210 (14 decks)

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