Immunomodulators (complete)

Question 1

What are monoclonal Abs? Describe how they are made.

Answer 1

• Essentially Abs that are made in a lab, but used in a human’s immune system
• Progeny of a single B cell => then fused w/ a multiple myeloma tumor cell => hybrid
• Hybrid grows forever in culture (like tumor cell), but produces the specific Ab of the B cell

Question 2

Why does the single B cell of the monoclonal Ab need to fuse with a tumor cell?

Answer 2

Otherwise the B cell would die quickly in culture

Need the opposite property => fusion w/ tumor cell (has that needed property)

Question 3

Discuss the use of monoclonal Abs as anti-inflammatory agents

Answer 3

Some tx are monoAbs to inflammation factors like TNF-alpha

IVIG can bind inhibitory Fc receptors on inflammatory cells

Infliximab: used in Crohn, UC, RA, ankylosing spondylitis

Adalimumab (Humira): used in RA, JRA, UC, Crohn, ankylosing spond, psoriasis

Question 4

What is a murine monoclonal Ab?

Answer 4

A mouse only monoAb

Question 5

What is a chimeric monoclonal Ab?

Answer 5

• Mouse VL/VH domains, human C domains

- Engineered at the DNA level

Question 6

What is a humanized monoclonal Ab?

Answer 6

• only mouse CDRs on V domain

- Engineered at the DNA level

Question 7

What is a human monoclonal Ab?

Answer 7

Fully human!

• To make this you need to “rent” a mouse w/ SCID => add human thymus, lymph node, and BM
• Ex: Humira

Question 8

What are the disadvantages of murine monoclonal Abs?

Answer 8

Human anti-mouse antibody (HAMA)

• Will result from second exposure to the monoAb
• If it doesn’t work the first time, don’t give it a second time

Question 9

What are the disadvantages of chimeric monoclonal Abs?

Answer 9

HACA

• Will result after too many exposures to this monoAb

Question 10

What are the disadvantages of humanized monoclonal Abs?

Answer 10

HAHA

• This eventually will happen after prolonged exposure to this monoAb

Question 11

What are the disadvantages of human monoclonal Abs?

Answer 11

• Dr. Cohen’s heard of people developing immunity against this, but not likely
• Need to have a super long exposure to do this, theoretically

Question 12

What are NK cells?

Answer 12

• Large granular lymphocytes (LGL)
• Make up 5-10% of blood lymphocytic cells
• Have mechanisms similar to CTL
• However! they do not have rearranged V(D)J genes and not-thymic derived!

Question 13

What is ADCC?

Answer 13

Ab-dependent cell-mediated cytotoxicity

• Not all tumor cells express markers that NK cells recognize via NK receptors
• Ab against tumor is added w/ NK cells
• NK cells have receptors for Fc end of IgG
• This is an Ab dependent way to interact with target cells

Question 14

Describe the effect of Class I MHC expression levels on susceptibility of target cells to CTL cells

Answer 14

CTLs can only target cells with Class I MHC expression

Question 15

Describe the effect of Class I MHC expression levels on susceptibility of target cells to NK cells

Answer 15

• NK cells can target these and also others
• They do not require the presence of this MHC to kill!
• However, they are downregulated in the presence of MHC Class I b/c technically it’s the CTL’s job to kill those guys

Question 16

Describe the mechanism for ADCC

Answer 16

• IgG binds to target cell
• NK cells binds to Fc end of Ab using it’s receptor
• NK cell now triggered => send lethal signals to target
• APOPTOSIS

Often the Ab used is a monAb

Question 17

Discuss the use of growth factors in BM transplantation

Answer 17

G-CSF and GM-CSF are used in BM transplants

sorry, not sure what else to say here

Question 18

Describe how a monoAb against a T cell surface molecule could enhance the activity of a CTL

Answer 18

• Remove T cells => transform them using lentivirus vectors with chimeric Ag receptor
• Ab linked to CAR
• Allows for a transformed CTL to bind to a tumor target w/ high affinity and chosen specificity

Question 19

Discuss the use of modified (drugs, isotopes) monoAbs in tumor diagnosis or therapy

Answer 19

• monoAbs can be targeted to specific tumor cells
• Some activate complement=> tumor lysed/phagocytosed
• More invoke ADCC
• can also be tagged w/ a poison or radioisotope

radioisotope tagging is used in diagnosis