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PMCOL 344 > Immune-4 > Flashcards

Immune-4 Flashcards

1
Q

what are 2 main drug classes

A

biologics and small molecules

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2
Q

what is the size of small molecules

A

less than 900Da (low MW)

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3
Q

what is the structure of small molecules

A

well defined

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4
Q

what is the target of small molecules

A

well known receptors or enzymes

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5
Q

what are biologics

A

pharmaceutical drug product manufactured in, extracted from, or semi synthesized from biological sources

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6
Q

what are some examples sources of biologics

A

blood, blood products, cells, tissues, organs, xenographs, gene therapies, vaccines, biotechnology

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7
Q

what are xenographs

A

transplantation of living cells, tissues or organs from one species to another

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8
Q

what are 3 examples of targeted therapeutic proteins (recognize the target specifically)

A
  • antibodies
  • antibody fusion proteins
  • antibodies conjugates
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9
Q

what are therapeutic antibodies based on

A

normal functions of immunoglobulins

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10
Q

what are 3 normal functions of immunoglobulins

A
  • circulate in blood and lymphatic system
  • bind to antigens expressed on cells
  • cells bound to antibodies are marked for destruction by macrophages and complement
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11
Q

what are 2 examples of using antibodies therapeutically

A

bind to human antigens (cancer)

neutralize growth factors

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12
Q

which is the fab domain

A

antigen binding fragment, complementariyy determining regions, define antigen specificity

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13
Q

which is the fc domain

A

has binding domains for comlement fixation and binding to cellular Fc receptors

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14
Q

what is in the light chain

A

1 variable region and 1 constant region

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15
Q

what is in the heavy chain

A

1 variable region and 3 constant regions

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16
Q

what is the difference between polyclonal and monoclonal antibodies

A

poly makes it have the affinity for the same antigen but different epitopes, monoclonal is just one epitope

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17
Q

what is an epitope

A

Epitope = the part of an antigen molecule to which an antibody attaches itself

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18
Q

does one antigen have many or one epitope

A

many

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19
Q

what are the 4 types of monoclonal antibodies and the %

A

murine(0%), chimeric(65%), humanized(>90%), fully human(100%)

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20
Q

which monoclonal antibody has the highest potential for immunogenecity

A

murine

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21
Q

which monoclonal antibody has the lowest potential for immunogenecity

A

fully human

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22
Q

which monoclonal antibody is omab

A

murine

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23
Q

which monoclonal antibody is ximab

A

chimeric

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24
Q

which monoclonal antibody is zumab

A

humanized

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25
Q

which monoclonal antibody is umab

A

fully human

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26
Q

what do you call chimeric antibody

A

ximab

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27
Q

what do you call humanized antibody

A

zumab

28
Q

what do you call fully human antibody

A

umab

29
Q

what do you call murine antibody

A

omab

30
Q

what do chimeric monoclonal antibody contain

A

antigen binding variable regions from immunized animals grafted onto human constant regions

31
Q

what % of each animal in chimeric

A

33% mouse and 67% human

32
Q

what kind of antibodies do chimeric monoclonal antibody make (but not much of)

A

human anti mouse antibodies (HAMA)

33
Q

how fast are chimeric monoclonal antibody cleared from the body

A

more slowly

34
Q

what kinda mechanisms do chimeric monoclonal antibody tend do engage

A

indirect (idk)

35
Q

what do humanized monoclonal antibody contain

A

only rodent complementary determining region of the original antibody grafted onto a human antibody framework

36
Q

what is the half life of humanized monoclonal antibody

A

long

37
Q

do humanized monoclonal antibody have HAMA

A

minimal

38
Q

do humanized monoclonal antibody maintain antigen recognition qualities

A

yes

39
Q

do humanized monoclonal antibody or chimeric have more HAMA

A

chimeric

40
Q

what is the structure of fully human monoclonal antibodies

A

100% human

41
Q

do fully human monoclonal antibodies activate the immune system

A

no

42
Q

what are 4 direct actions of mAB based therapy

A
  • ligand blockage
  • receptor blockage
  • receptor downregulation
  • signalling induction
43
Q

what are 3 mechanisms of indirect cell death/ cell depletion of mAB based therapy

A
  • antibody dependent cellular toxicity (ADCC)
  • complement dependent cytotoxicity (CDC)
  • complement dependent cellular cytotoxicity (CDCC)
44
Q

what does indirect mAB based therapy cause

A

depletion, cell death

45
Q

what mediates the indirect mAB based therapy mechanisms

A

the immune system

46
Q

which is the indirect mechanism that most mAB engage in

A

antibody dependent cellular toxicity (ADCC)

47
Q

are mAbs able to activate the classical complement pathway and why

A

no because they are unlikely to reach surface density

48
Q

what happens in antibody dependent cellular toxicity (ADCC)

A

-antibodies against surface proteins, binds to target, Fc receptors bring on natural killer cells and macrophages to kill the target cell

49
Q

what happens in complement dependent cytotoxicity (CDC)

A

Antigen recognized by antibody, antibody on surface of target cell, the antibody activates the complement
Forms the MAC which lyses the target cells

50
Q

what happens in complement dependent cellular cytotoxicity (CDCC)

A

Antibody activates complement which activates cells - the immune cells(natural killer cells and macrophages) have receptors which are put there by complement

51
Q

what is a pro to small molecules

A

more convenient to administer (oral)

52
Q

what is a con to small molecules

A

extensive plasma concentrations variation among patients

53
Q

what is the main pro to mAbs

A

they are a lot more specific (facilitates precise action, associated with less toxicity)

54
Q

what is another pro to mAbs besides specificity

A

they they have longer half lives, so infrequent dosing

55
Q

what are 2 cons to mAbs

A
  • needles

- poor ability to penetrate into tissues and tumors

56
Q

can mAbs cross the BBB

A

no

57
Q

are human or chimeric more specific

A

the same

58
Q

what are recombinant fusion proteins

A

chimeric bi-functional proteins

59
Q

what composes recombinant fusion proteins

A
  • antibody or antibody fragment (Fc)

- functional effector molecule (receptor, ligand)

60
Q

how are all recombinant fusion proteins named

A

with “cept” at the end

61
Q

what are fused in recombinant fusion proteins

A

the binding site of receptor to the antibody Fc

62
Q

what do recombinant fusion proteins act as

A

decoy receptor

63
Q

are recombinant fusion proteins small molecules or biologics

A

biologics

64
Q

what does it mean that recombinant fusion proteins work as decoy receptors (example)

A

Give fusion protein with receptor for TNF
-Instead of binding to receptor on cell, it will bind to the decoy protein
Mostly for blocking

65
Q

what does the Fc region do for recombinant fusion proteins

A

it improves the proteins half life and other pharmacological properties

66
Q

are recombinant fusion proteins or antibodies more expensive

A

recombinant fusion proteins

PMCOL 344 (27 decks)

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