A10 - Immunomodulation and Immunotherapy

What do prophylactic cancer vaccines do?

Allow the immune system to effectively protect against cancer development.

• E.g. Immunise with tumour-specific antigens

• E.g. Immunise with cross-protective antigens

What type of vaccine is the cervical cancer HPV vaccine and what does it use?

Recombinant vaccine which uses Saccharomyces cerevisiae to generate virus like particles to produce a strong antibody response

What type of vaccine is the Hepatitis B vaccine and what does it use?

Recombinant vaccine which uses Hep B surface antigen

How is Provenge made and what is it used to treat?

Created using patient’s dendritic cells and tumour cells.

Treats metastatic prostate cancers.

What type of vaccine is the Bacillus Calmette-Guerin (BCG) vaccine and what does it treat?

Adjuvant vaccine

Used to treat bladder cancers which internalise antigens.

What are adjuvants and why are they used?

Used in vaccines to increase immune response

• Especially in non-live vaccines

Most antigens are poorly immunogenic so adjuvants can help increase the immune response against them

What are some examples of adjuvants?

• Aluminium salts

• MF-59

• Bacteria components

• Freund’s complete adjuvant

  • Banned in humans due to toxicity

What type of adjuvant is banned in humans due to toxicity?

Freund’s complete adjuvant

What is desensitisation treatment?

Involves weekly injections of increasing dosage of allergen over 14-18 weeks.

Aims to desensitise an individual against an allergen to prevent allergic reactions.

Desensitisation treatment causes a switch from an Ig_ response to an Ig_ response. Fill in the gaps.

Causes a switch from an IgE response to an IgG response

What is cytokine therapy?

Small <20kDa cytokines given to an individual

• Induces interleukins and interferons

Diverse range of effects

What is G-CSF therapy and what type of immunotherapy is it?

Type of cytokine therapy.

Stimulates neutrophil development and differentiation

• Also increases number of haematopoietic stem cells in blood

What can monoclonal antibody therapies be used for?

Can be used to treat:

• Cancers

• Allergies

• Autoimmune diseases

• Etc

What is Muromonab and what does it do?

Mouse derived antibody against human CD3e

Prevents activation of kinase and cascade events which cause T-cell activation

What is Basiliximab and what does it do?

Antibody against human CD25

Blocks IL-2 induced T-cell proliferation by preventing IL-2 binding to its receptor

What is Daclizumab and what does it do?

Anti-human CD25 antibody

Blocks IL-2 induced T-cell proliferation (same as Basiliximab)

• However, not used anymore as it caused encephalitis

What is Infliximab (Remicade) and what does it do?

Anti-TNF-alpha antibody

Used to treat RA and Crohn’s disease

• However only works in 50% of people and 3 months of treatment is needed to see if it works

What is Pembrolizumab (Keytruda) and what does it do?

Anti-PD1 antibody (Programmed death receptor)

Prevents binding of PD1 to PD-L1 which ‘turns on’ T-cells so they attack cells expressing PD-L1.

What is immunoglobulin replacement therapy?

Intravenous immunoglobulin therapy

2-3 weekly infusions of IgG from pooled human plasma (3000-6000 donor units)

What can a Haemopoietic stem cell transplantation (HSCT) be used to treat?

• Severe Combined Immunodeficiency (SCID)

• Neutrophil disorders

• Bone Marrow failure

• Lymphoma

• Leukaemia

What are some sources of haemopoietic stem cells?

Sources

• Peripheral blood

• Bone marrow

• Foetal cord

What is an Autologous stem cell transplant?

Taking stem cells from the patient’s body and transplanting them back in

What is an Allogenic stem cell transplant?

Taking stem cell from a matched sibling or unrelated donor and transplanting them into the patient

What is gene therapy?

Replacement of defective genes with normal genes in self-replicating stem cells

What are Glybera and Strimvelis?

Two gene replacement therapies which are licensed in Europe.

What gene replacement therapy can be used for Severe Combined Immunodeficiency and what gene does it replace?

Strimvelis can be used for SCID treatment.

Replaces the defective ADA gene.