Immunotherapy

Question 1

types of immunosuppression

Answer 1

General immunosuppressive strategies
• Allergy and autoimmune disease
• Blanket immune suppression
• Opportunistic infections
• Strong need to develop tailored therapies that target the specific immune response but leave the rest of the immune system free to fight disease

Question 2

with a diagram describe the methods for inhibiting t cell activation to treat graft rejection

Answer 2

see notes

Question 3

active adaptive immunity

Answer 3

infection/exposure

immunisation vaccines

Question 4

passive adaptive immunity

Answer 4

placental transfer of IgG
colostral transfer of IgA
IG therapy or immune cells

Question 5

examples of passive immunity

Answer 5

snake or spider bites, scorpion or fish stings - passive infusion of antibody specific for the toxin
hypogammaglobulinaemia - primary or secondary infusion of g-globulins to reduce infection
rabies IG - PEP together with caccination

Question 6

examples of immunoglobulin for PEP

Answer 6

Human Normal Immunoglobulin (HNIG)
Hepatitis A
Measles
Polio
Rubella

Specific Immunoglobulins
Hepatitis B
Rabies
Tetanus
Varicella-Zoster Virus

Question 7

what is IVIg?

Answer 7

• 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 8

licensed indications for IVIg

Answer 8

Primary immunodeficiency
Wiskott Aldrich syndrome
IgG subclass deficiencies with recurrent infections
Idiopathic Thrombocytopenic Purpura
Kawasaki disease
Common variable immunodeficiency
Multiple myeloma/CLL
Children with HIV
Guillain-Barre syndrome
Allogenic bone marrow transplantation—prevention of graft
versus host disease (GVHD) and infections

Question 9

direct immunotherapy

Answer 9

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 10

target for direct immunotherapy

Answer 10

the tumour

Question 11

indirect immunotherapy

Answer 11

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

Question 12

target for indirect immunotherapy

Answer 12

immune system

Question 13

examples of direct immunotherapy

Answer 13

Monoclonal antibodies
Chimeric antigen receptors (CARs)
Bi-specific antibodies

Question 14

examples of indirect immunotherapy

Answer 14

Tumour vaccines
Dendritic cell vaccines
Adoptive cell transfer
Cytokine therapies
Checkpoint inhibitor therapies
Stimulatory antibodies

Question 15

describe cytokine therapies

Answer 15

• Immunomodulatory cytokines to activate anti tumour immunity
• pegylated IFN-a, IL-2, GM-CSF
• Used in specific cancers
• Pegylated is an effective anti-viral IFN-a therapy and used in melanoma

Question 16

polyclonal vs monoclonal antibodies

Answer 16

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
Typical antibody response: in humans pathogenic insult, vaccines etc. - polyclonal
Antibodies with different Variable regions bind multiple epitopes

Question 17

making monoclonal antibodies

Answer 17

immunisation
fusion + immortalisation of B cells
isolation and screening
expansion of desired hybridoma

Question 18

discuss rituxan (rituximab)

Answer 18

• First line treatment for non-Hodgkin’s lymphoma
• Specific for the CD20 molecule on the cell surface of a small sub-population of B cells
• Crossover mAb
– Originally developed for NHL and lymphoma but now found to have highly beneficial effects in rheumatoid arthritis and probably systemic lupus erythematosus (SLE)

Question 19

with a diagram show how rituximab works

Answer 19

see notes

Question 20

discuss infliximab (anti-TNF therapy)

Answer 20

• First approved November 1999 for the treatment
of rheumatoid arthritis
• Now used to treat several other AI diseases
– Ankylosing spondylitis
– Crohn’s disease
– Ulcerative colitis
• Chimeric antibody that blocks the function of
tumour necrosis factor alpha (TNF)
– TNF is a pro-inflammatory cytokine that stimulates
an acute phase reaction

Question 21

discuss herceptin

Answer 21

Trastuzumab
• Approved in 1998 (USA) for treatment of human growth epidermal growth factor receptor 2
(HER2) positive metastatic breast cancer
– Previously HER2+ sufferers had a very poor prognosis
• The antibody binds HER2 on cancer cells and marks them out for destruction by the immune system
• 15-20% of breast cancer cases are HER2+

Question 22

how does pertuzumab differ from trastuzumab

Answer 22

directed at the dimerisation domain of HER2 - disruption of dimer formation

Question 23

discuss checkpoint inhibitors

Answer 23

Checkpoint inhibitor antibodies unlock the gateway to the adaptive immune system
• Powerful anti-tumour responses
• But potential for immune related adverse effects

Question 24

discuss CAR T cell therapy

Answer 24

• CAR T cell are engineered to
express antigen-targeted receptors
specific for tumour antigens.
• CAR includes an antigen-binding
domain fused to a transmembrane
domain followed by T-cell
activation domains associated with
the T-cell receptor (TCR).
• A T cell modified with a CAR is
endowed with a new antigen
specificity, and binding its antigen
supports T-cell activation and killing
of the target cell.