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Immune missing > 4- Monoclonal antibodies > Flashcards

4- Monoclonal antibodies Flashcards

1
Q

structure of an antibody

A

FAB- antibody binding fragment. at top. hyper-variable regions that allow for recognition of virtually unlimited array of antigens

FC- at bottom. fragment crystallisable region. responsible for binding of immune effector cells to illicit the immune response

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2
Q

what are monoclonal antibodies

A

Monoclonal antibodies recognise only one epitope i.e they are monovalent and are produced from a single B- lymphocyte clone which will produce an antibody specific for one particular antigen

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3
Q

describe development of monoclonal antibodies

A

A mouse was injected with an antigen to elicit a specific immune response. The spleen was then removed and the B cells isolated, these were then fused with an immortalised myeloma cell line (hybridoma) which then produced the antibody that the mouse B cell was specific for, which is then screened for and purified for use.

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4
Q

example of chimeric antibodies

A

rituximab

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5
Q

what are bispecific antibodies

A

bind to two different cell populations eg. a cancer cell and a T cell. can redirect the immune system against cancer

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6
Q

what are conjugated monoclonal antibodies

A

combined with a. therapeutic drug or. chemotherapy particle

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7
Q

4 ways monoclonal antibodies can work

A

• Binding to induce cell death

• Binding with cell surface receptors to activate:
antibody-dependent cell-mediated cytotoxicity or
complement-dependent cytotoxicity (CDC)

• Internalization (ie being taken in by the cell
through the membrane) for antibodies delivering
toxins into the cancer cell

• Blocking inhibitory effects on T cells (checkpoints).
Thus activating T cells to help ‘kill’ the cancer cells

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8
Q

what can antibody binding result in

A

cell death induction, antibody dependent cell mediated toxicity activation (ADCC), complement dependent cytotoxicity (CDC)

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9
Q

what is antibody dependent cell mediated toxicity activation (ADCC)

A

the FC region activates immune effector cells causing cell lysis

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10
Q

what is complement dependent cytotoxicity (CDC)

A

complement activation causes formation of MAC and therefore cell lysis

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11
Q

what is MAC

A

membrane attack complex

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12
Q

how can monoclonal antibodies be used in diagnostics

A

use of emission of light (fluorescent tag), enzymatic reaction (enzymatic tag)

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13
Q

what is lymphoma

A

B and T cell neoplasms. clonal proliferations of lymphoid cells. causes enlargement of lymph cells, liver, skin, testes, bone marrow or bowel

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14
Q

what are symptoms of lymphoma

A

night sweats, fevers, weight loss

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15
Q

what are two types of lymohoma

A
  • small clonal B lymphocytes which retain the follicular pattern Follicular lymphoma (low grade)
  • larger clonal B lymphocytes which take over the node in a diffuse pattern. Diffuse large B cell lymphoma (high grade)
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16
Q

what do mature B cells express

A

CD20

17
Q

treatment strategies lymphoma

A 
Chemotherapy (more for B cell)
• Radiotherapy
• Monoclonal antibody therapy 
• Emerging  new targeted therapy 
• Stem cell transplantation
18
Q

side effects of monoclonal antibodies

A
  • mild/no symptoms

- severe infusion related reaction

19
Q

how to manage infusion related reaction

A
  • pre-medication with steroid, anti-histamine, paracetemol

- slow infusion rate at first

20
Q

what monoclonal antibodies solid cancer

A

trastuzumab- HER2
bevacizumab- VEG-F
nivolumumab- CLTA-4

21
Q

what monoclonal antibodies autoimmune

A

Infliximab and Adalimumab – inhibition of TNF-alpha

22
Q

which monoclonal antibodies cardiology

A

Abciximab – inhibition of platelet glycoprotein IIb/IIIa

23
Q

which monoclonal antibodies Endocrine

A

Denosumuab – inhibition of RANK ligand on osteoclasts

24
Q

most common haematological malignancy

A

diffuse large B cell lymphoma

25
Q

diagnosis lymphoma

A

-biopsy and CD20 histochemistry

26
Q

how do antibody drug conjugates work

A
  • very potent cytotoxic drug bound by a linker to a monoclonal antibody
  • linker inactivates MAB in circulation
  • binds to tumour antigen
  • receptor mediated endocytosis
  • relelase of toxic agent
27
Q

positives of antibody drug conjugates

A
  • monoclonal antibodies can have own anticancer properties such as preventing signalling, antibody dependent cell cytotoxicity and induction of apoptosis
  • drug used is 1000x more potent
  • prolonged exposure to tumor cell and internalisation (due to linker)
28
Q

how to bispecific MAB work

A

recognises and binds to B cells via CD20 and t cell via CD3. t cell activates.

secretes peforin which creates pores in b cell, and then inserts granzymes through pore which induces apoptosis.

29
Q

describe progression of symptoms in history for follicular lymphoma (low grade) vs diffuse large cell lymphoma (high grade)

A

low grade- slow

high grade- rapid

Immune missing (1 decks)

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