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Immunology > 3.2.2 Types Of Monoclonal Antibdoies > Flashcards

3.2.2 Types Of Monoclonal Antibdoies Flashcards

1
Q

What is immunogenicity?

A

Ability of a foreign substance e.g. antigen, to provoke an immune response

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2
Q

What are the different types of monoclonal antibodies?

A

Murine 0% human, extremely high risk -omab suffix
Chimeric 65% human, high risk -ximab suffix
Humanised >90% human, low risk -zumab suffix
Fully Human 100% human, very low risk-umab suffix

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3
Q

What are conjugated monoclonal antibodies?

A

Antibody, linker and cyotoxic compound

Cytotoxic compound delivered directly to cell targeted by monoclonal antibody causing cell death

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4
Q

What are the benefits of conjugated monoclonal antibodies?

A

Persist in circulation
Can be internalised by cancer cells

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5
Q

How are conjugated MABs internalised?

A

Via receptor mediated endoycytosis

Lysosomes degrade the antibody and the cytotoxic contents are released

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6
Q

What are bispecific monoclonal antibodies?

A

Both arms of the Fab regions normally bind to the same thing

Bispecific monoclonal antibodies the two arms are able to bind to 2 different things, effector T cell and B cell

Used in B cell lymphomas

Antibody brings B and T cells together, T cell then stimulated and attacks B cell bound to other arm by releasing perforin

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7
Q

What receptors do MABs bind to on T and B cells in bispecific MABs?

A

B cell- CD20
T cell- CD3

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8
Q

How do MABs attack cancer?

A
  • Binding with cell surface receptors to activate or inhibit signalling within the cell
  • Binding to induce cell death
  • Binding with cell surface receptors to activate, antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC)
  • Internalisation for antibodies delivering toxins into the cancer cell
  • Blocking inhibitory effects on T cells, thus activating T cells to help kill cancer cells
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9
Q

How do checkpoint inhibitors work?

A

Inhibition present on T cells to stop immune system from damaging itself

Cancer usually increases inhibitory effects on T cells, meaning the cancer isn’t targeted by T cells

If this inhibiton is stopped then T cells can kill cancer cells

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10
Q

What is cluster of differentation classification?

A

Anitgens can be grouped together allowing cells to have an immunophenotype

Cancer cells have specific immunophenoytpes, thus they can be targeted

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11
Q

What type of cancer is lymphoma?

A

Hodgkins- B cells only
characterised by Reed-Sternberg cells

Non-
Hodgkins- B or T cell neoplasms

Lymphoma typically causes enlargement of lymph nodes

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12
Q

What other areas can be affected by lymphoma?

A

Extra-nodal areas:
Spleen
Bone marrow
Liver
Skin
Testes
Bowel

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13
Q

What do people with lymphoma often complain of?

A

Drenching night sweats
Fevers
Weight loss, more than 10% over 6 months
Dry cough- hilar lymph nodes affected
Early satiety- enlarged spleen compresses stomach

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14
Q

What are the two types of B cell lymphomas?

A

Follicular lymphoma
- Lymph node taken over by small clonal B lymphocytes which retain their follicular pattern

Diffuse large B cell lymphoma
- Lymph node taken overy by larger clonal B lymphocytes
- Take over the node in a diffuse pattern

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15
Q

What CD do follicular lymphoma and diffuse large b cell lymphoma have?

A

CD20

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16
Q

How is lymphoma staged?

A

Ann Arbor staging

17
Q

What imaging is used to detect lymphoma?

A

Positron Emission Tomography- PET scan

Lymphomas are highly metabolically active so they show up very well on PET scans

18
Q

How is lymphoma diagnosed?

A

Biopsy

19
Q

How is treatment determined for lymphoma?

A

Immunohistochemistry on biopsy sample to detect the CDs present to check susceptibility

20
Q

What treatment stratergies are used for lymphoma?

A

Chemotherapy- combined, non-overlapping toxicity

Raidotherapy- local parts of body, used early or for symptom control

Monoclonal antibody therapy

New targeted therapy

Stell cell transplantation- allogenic (someone else), autologous (self)

21
Q

Give an example of a MAB against CD20

A

Rituximab

22
Q

Why are MABs used in lymphoma?

A

Significantly improved complete response rates to chemotherapy

Significantly improved survival

23
Q

What are the side effects of MABs?

A
  • No symptoms or mild, e.g. fatigue
  • Mild reaction to 1st infusion then tolerate treatments after
  • Severe infusion related reactions as immune system reacts to foreign protein
24
Q

What happens if you infuse MABs too quickly?

A

Hyperventilation
Nausea/vomiting
Shivering
Back pain
Heavy chest

25
Q

What can be given to stop nausea due to MABs?

A

Metoclopramide and IV steroids

Antihistamines to stop facial flushing

26
Q

What is involved in patient education with managing infusion related reactions?

A

Patient education
- Explain to the patient they may still have side effects after premedication
- Tell patient to inform staff of any change so staff can take immediate action
- Tell patient to stop anti-hypertensives for 12 hours prior to infusion

27
Q

What pre-medications should be given to prevent reactions?

A

Steroids
Anti-histamines
Paracetamol

28
Q

How should infusions be given to stop reactions?

A

Infusions started slowly, increased if they are tolerated

Drugs to stop reactions should be given prior to starting treatment

29
Q

What MABs are given for solid cancer?

A
  • Trastuzumab – inhibition of HER-2 signalling
  • Ipilimumab – inhibition of CTLA-4 signalling
  • Nivolumab/Pembrolizumab – inhibition of PD1 signalling (checkpoint inhibitors)
30
Q

What MABS are given for autoimmune conditions?

A

Infliximab and Adalimumab – inhibition of TNF-alpha

31
Q

What MABs are given in cardiology?

A

Abciximab – inhibition of platelet glycoprotein IIb/IIIa

32
Q

What MABs are given for respiratory conditions?

A

Mepolizumab – inhibition of IL-5

33
Q

What MABs are given in dermatology?

A

Ustekinumab – inhibition of IL-12 and IL-23

Immunology (14 decks)

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