DA: Exam 4 Lecture 3- Biologics Antibodies and Drug Conjugates- Shaw Dawg

antibodies are

immunoglobulins

Antibodies are produced from _______ cells in the immune system

b

what do antibodies react with

a single, specific protein

T/F: antibodies can bind with multiple proteins

F- only 1

what does each antibody consists of

4 polypeptides- 2 heavy and 2 light chains joined to form a "Y" shaped molecules

what is defined as multiple peptides bound together

polypeptides

T/F: the amino acid sequence in the tips of the "Y" is the same in different antibodies

F: varies greatly

how many amino acids is the "Y" region composed of

110-130

what gives an antibody specificity for binding antigen

the varying amino acids composed in the variable region

treating the antibody with ______ can cleave the variable region

protease

when a protease cleaves the variable region what does it produce

Fab or fragment antigen binding

T/F: Fab includes the variable ends of the antibody

t

what region determines the mechanism used to destroy antigen

constant region

what region of an antibody decides the immune mechanism

constant region

what are the 5 major classes that antibodies are divided into

IgM, IgG, Iga, IgD and IgE

what determines which antibody class the antibody will be in

based on their constant region structure and immune function

why are antibodies recruited

the immune system to identify and neutralize foreign objects like bacteria and viruses

what type of foreign objects do antibodies neutralize

bacteria and viruses

T/F: each antibody has a unique target known as the antigen present on the invading organism

t

what is the key that helps the antibody in identifying the organism

antigen present

how does the antigen present help the antibody identify organisms

both the antibody and the antigen have similar structure at the tips of their "Y" structures

T/F: antibodies can have multiple antigen keys

F: just like every lock has a single key, an antibody has a single antigen key.

what happens when the antigen present is inserted into the antibody

the antibody activates, tagging or neutralizing its target

what is the main function of humoral immune system

production of antibodies

what type of cells activate immune system for an immune response

t cells

what is defined as any foreign substance that elicits an immune response

antigens

what is defined as the specific region on an antigen that an antibody recognizes and binds to

epitope or antigenic determinant

what is another term for epitope

antigenic determinant

where is the epitope always located

on the outside of the antibody

how many amino acid long chains are on the surface of the epitope

5-8

T/F: on an epitope the chain of amino acids exist in a 2D structure

F: only appears as a 3D structure

what is the native form of an epitope

3D

T/F: an epitope may only be recognized in its form as it exists in solution?

t: 3D

what is defined as antibodies that are made by identical immune cells that are all clones of a unique parent cell

monoclonal antibodies (mAb or moAb)

are mouse antibodies useful for treatment of humans

no

what needs to be done to the mouse antibodies to be useful in the treatment of humans

create monoclonal antibodies that are good for humans

mouse antibodies can now be injected into humans when in this form

what are the abbreviations for monoclonal antibodies

mAb or moAb

T/F: monoclonal antibodies can bind to the same epitope

t: known as monovalent affinity

T/F: polyclonal antibodies can bind to multiple epitopes

t

what type of cells make up polyclonal antibodies

plasma cell (antibody secreting immune cell) lineages

what type of monoclonal antibodies can be engineered, by increasing the therapeutic targets of one single monoclonal antibody to 2 epitopes

bispecific monoclonal antibodies

bispecific monoclonal antibodies can be engineered by increasing __________ of one single monoclonal antibody to 2 epitopes

therapeutic targets

bispecific monoclonal antibodies can be engineered by increasing therapeutic targets of one _________ to 2 epitopes

single monoclonal antibody

bispecific monoclonal antibodies can be engineered by increasing therapeutic agents of one single monoclonal antibody to 2 _______

epitopes

how are chimerization of mice achieved

adding the human constant domain to mouse variable region

how do we obtain humanization of mouse antibodies

in addition to adding the human constant domain, it is possible to carry out grafting of complementary determining regions

how can we distinguish a human antibody producing mouse

if the mouse has the ability to produce human monoclonal antibodies

T/F: for a human antibody producing mouse the human heavy and light chain variable genes have been cloned into mouse

t

T/F: for a human antibody producing mouse the mouse heavy and light chain variable genes are joined with the human

F: they have been knocked out

who owns the humanized monoclonal antibodies

mederax and abgenix

extracellular binding to an antigen is _______ for a targeted protein

specific

how are most therapeutic actions of antibodies used to treat cancer

extracellular binding to an antigen

extracellular binding to an antigen can produce/inhibit downstream signaling

inhibit

T/F: extracellular binding to an antigen is inhibited especially if antigen is critical for tumor cell growth

t

extracellular binding to an antigen can induce what 2 types of cellular cytotoxicity

antibody-dependent (ADCC)

complement dependent (CDC)

T/F: extracellular binding to an antigen can cause apoptosis

t

how is Herceptin used in the treatment of cancer

targets the Anti-HER2/Neuu growth factor receptor in breast cancer

how is Genentech used in the treatment of cancer

targets the Anti-HER2/Neuu growth factor receptor in breast cancer

how is Erbitux used in the treatment of cancer

targets the antibody to epidermal growth factor receptor

T/F: Herceptin and Erbitux are used in the treatment of breast cancer

t

how is Avastatin used in the treatment of cancer

targets the antibody to vascular-endothelial growth factor receptor (anti-angiogenesis theraypy)

which cancer treatment is an example of anti-angiogenesis therapy

Avastin

what does epidermal growth factor stimulate

growth and cell division

what is the main cause of breast cancer

EGFR

what does EGFR cause, which leads to breast cancer

uncontrolled growth

T/F: cancer cells require a lot of sugar

t

why do cancer cells require a lot of sugar

energy source

what does a blood tumor stimulate

VEGF

what does VEGF stimulate

angiogenesis

angiogensis

formation of new blood vessels

Brentuximab

Vedotin

T/F: when Brentuximab is administered it is stable in the blood stream

t

what is described as an antibody-drug conjugate (ADC) that targets CD30

brentuximab

what does brentuximab target

CD30

CD30 is a defining marker of what

classical hodgkin lymphoma (HL)

what attaches an anti-CD30 monoclonal antibody to a cytotoxic agent

protease-cleavable linker

what cytotoxic agent is the anti-CD30 monoclonal antibody attached to

monomethyl auristatin E (MMAE)

what is the purpose of the anti-CD30 attachment to MMAE

to be stable in the bloodstream but to release MMAE when internalized into CD30-expressing tumor cells

what results when MMAE is released

target cell death