Immunotherapy

Question 1

Immunosuppression

Answer 1

Used in allergy and autoimmune disease. Blanket immune suppression (suppress teh immune reponse). Risk of opportunistic infections.

Question 2

Acute transplant rejection

Answer 2

Acute rejection in particular is associated with T cell responses that mediate immune cell infiltration into the graft and effect its rejection

Question 3

Cyclosporin FK506

Answer 3

Inhibits phosphatase calcineurin. This dephosphorylates and activates the T-cell transcription factor NFATc,

Question 4

Rapamycin

Answer 4

Inhibits mTOR

Question 5

Passive Adaptive immuntiy

Answer 5

Placental transfer of IgG
Colostral transfer of IgA
Immunoglobulin therapy or immune cells

Question 6

Advantages of passive immunity treatment

Answer 6

Gives immediate protection

A quick fix

Question 7

Disadvantages of passive immune treatment

Answer 7

Short term effect – no immunological memory
Serum sickness – incoming antibody is recognised as a foreign antigen by the recipient and results in anaphylaxis
Graft versus host disease (cell grafts only) – incoming immune cells reject the recipient

Question 8

Snake or spider bites, scorpion or fish bites

Answer 8

passive infusion of antibody specific for the toxin

Question 9

Hypogammaglobinaemia

Answer 9

primary or secondary

Infusion of γ-globulins to reduce infection

Question 10

Immunoglobulin for post-exposure prophylaxis

Answer 10

Human Normal Immunoglobulin (HNIG)
	Hepatitis A
	Measles
	Polio
	Rubella
Specific Immunoglobulins
	Hepatitis B
	Rabies
	Tetanus
	Varicella-Zoster Virus

Question 11

IV immunoglobulins

Answer 11

Plasma-derived IgG is a key biologic for replacement therapy in primary and secondary immunodeficiency disorders
Also used for some autoimmune disorders
Polyclonal IgG preparation usually given intravenously (IVIg) but can also be applied subcutaneously (SCIg)
Very high dose - 1-3g/Kg
Source – pooled from several thousand donors (1,000 – 100,000)

Question 12

Indications for IVIg

Answer 12

Primary immunodeficiency 
Wiskott Aldrich Syndrome
IgG subclass deficiency with recurrent infections 
Kawasaki disease
ITP

Question 13

Direct Immunotherapy

Answer 13

Antibodies or antibody related fragments that detect an antigen on the tumour cell and destroy the target either by recruiting immune cells or by delivering a toxin or radioisotope to it

Question 14

Indirect Immunotherapy

Answer 14

The immune system is activated rendering it able to seek and destroy tumour cells

Question 15

Direct Immunotherapy examples

Answer 15

Monoclonal antibodies

Chimeric antigen receptors
(CARs)

Bi-specific antibodies

Question 16

Indirect Immunotherapy examples

Answer 16

Tumour vaccines

Dendritic cell vaccines

Adoptive cell transfer

Cytokine therapies

Checkpoint inhibitor therapies

Stimulatory antibodies

Question 17

Cytokine therapy

Answer 17

Immunomodulatory cytokines to activate anti-tumour immunity

Usually pegylated

Question 18

IFN-alpha

Answer 18

Cytokine therapy used in the treatment of melanoma

Question 19

IL-2

Answer 19

Cytokine therapy used in kidney cancer

Question 20

Polyclonal Antibodies

Answer 20

Polyclonal response: Immunisation with antigen will
typically lead to a polyclonal response

Many different B cell clones will generate antibodies
specific for the antigen

A number of epitopes will be bound by antibody

Question 21

Therapeutic Monoclonal Antobodies

Answer 21

Murine
Chimeric
Humanized

Question 22

Rituxan (Rituximab)

Answer 22

Monoclonal antibody specific for the CD20 molecule on the cell surface of a small sub-population of B cells. It is the first line treatment for non-hodgkins lymphoma. Also useful in rheumatoid arthritis.

Question 23

How does rituximab work

Answer 23

Recruits proinflammatory cells or activates the complement system killing the cell.

Question 24

Infliximab (anti-TNF alpha)

Answer 24

Used in ankylosing spondylitis, crohns, UC.

It blocks the function of tumour necrosis factor alpha (TNF-alpha)

Question 25

Herceptin (Trastuzumab)

Answer 25

The antibody binds HER2 on cancer cells and marks them out for destruction by the immune system

Treatment of human growth epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer
Previously HER2+ sufferers had a very poor prognosis

Question 26

Pertuzumab

Answer 26

Binds both HER2 and prevents dimerisation with HER3 receptor which adds another benefit to antibody therapy

Question 27

Check point inhibitors

Answer 27

Checkpoint inhibitor antibodies unlock the gateway to the adaptive immune system

Powerful anti-tumour response through immense activation of T cell

Potential for immune related adverse effects

Question 28

Anti-CTLA-4 antibodies (ipilimumab)

Answer 28

Dendritic cell are able to activate the T cell (best capable) via CD28 receptor. CTLA-4 ligand will shut it down. Outcompetes CD28. Ipilumimab blocks the relationship between CTLA4 and the T cell therefore allowing it to be fully activated.

Question 29

Anti-PD1/PD-L1 antibodies (Pembrolizumab)

Answer 29

PD-1 receptor ligand between the tumour cell and the t cell. This results in suppression of the T cell. By inhibiting PD-1 or the PD-1 ligand, the T cell will not be able to be suppressed.

Question 30

Dendritic Cell Vaccines

Answer 30

Take a blood sample from patient
Culture cells in vitro
With cytokines that promote APC function
Transfuse patients with APC after uptake of tumour antigen

Question 31

Chimeric Antigen Receptor T cells

Answer 31

Combine antibody and T cell response to improve immunity
Increases longevity & overcomes T cell tolerance mechanisms
Need to identify a tumour restricted antigen
Tumour escape if antigen no longer expressed

mainly used in lymphoma