Immuno: Immune modulating therapies Pt.2 Flashcards
List some examples of conjugate vaccines.
encapsulated bacteria
- Haemophilus influenzae type B
- Meningococcus
- Pneumococcus
What are adjuvants and descibe how they work.
Adjuvants increase the immune response to a vaccine
- They mimic the action of PAMPs on TLR and other PRRs
- Increases the immune response without altering its specificity
List some examples of adjuvants.
- Aluminium salts (MOST COMMON)
- Lipids (monophosphoryl lipid A)
How SARS-CoV mRNA vaccines work
- Infect E-coli with DNA for spike protein
- Harvest DNA and transcribe to mRNA
- Complexed with lipids, injected into arm
- Once injected, mRNA enters human cells which is then translated
- Spike protein then expressed by cells to stimulate immune response
What is another technique of SARS-CoV vaccination?
Adenovirus vector vaccines
What are dendritic cell vaccines?
- Used against cancer
- Dendritic cells collected from patient and exposed to tumour antigens to try and boost the immune response against the cancer
Give an example of a dentritic cell vaccine
Sipuleucel-T (Provenge)
- Used in prostate cancer
- Dendritic cells are harvested from patient and exposed to recombinant PAP-GMCSF (PAP is the tumour antigen, GMCSF stimulates the dendritic cell response)
- Dendritic cells reinfused back into patient to stimulate immune response
What is human normal immunoglobulin?
- Immunoglobulin prepared from thousands of pooled donors
- Covers wide range of unspecified antigens
- Contains pre-formed IgG
- Administered IV or SC
What is the aim of cytokine therapy and give some examples
Modifies immune response
Examples:
- IL-2 - stimulates T cells in renal cancer
- IFN-gamma - enhance macrophage function in CGD
- IFN-alpha - enhance antiviral response in hepatitis B and C
What are two therapies which replace missing immune system components?
- Hematopoietic stem cell transplantation (SCID, CML)
- Antibody replacement
What are the main indications for haematopoietic stem cell transplantation?
- Life-threatening immunodeficiency (SCID)
- Haematological malignancy
- Severe haematological disease (e.g. thalassaemia)
What is antibody replacement?
Normal human immunoglobulin
Pooled from >1000 healthy donors
Contains preformed IgG to a wide range of unspecified organisms
List some indications for antibody replacement
- Primary antibody defect
- X-linked agammaglobulinaemia
- X-linked hyper IgM syndrome
- Common variable immunodeficiency
- Secondary antibody defect
- CLL
- Multiple myeloma
- After bone marrow transplantation
When might specific immunoglobulin be given?
Passive immunity as post-exposure prophylaxis for:
- Varicella Zoster
- Tetanus
- Hepatitis B
- Rabies
Derived from donors with high plasma IgG titres to specific pathogens
List four types of T cell adoptive cell transfer (cellular immunotherapy)
- Virus-specific T cells
- Tumour infiltrating T cells (TIL)
- T cell receptor T cells (TCR)
- Chimeric antigen receptor T cells
Using an disease example, describe how virus-specific T cells therapy works
Used for EBV in patients who are immunosuppressed to prevent the development of lymphoproliferative disease
- Blood is taken from the patient or from a donor
- Peripheral blood mononuclear cells are isolated and stimulated with EBV peptides
- This creates and expansion of EBV-specific T cells which are then reinfused into the patient
NOTE: tumour infiltration T cell therapy follows the same principle but uses tumour antigens
Describe how tumour infiltration T cell therapy works
Same principle as virus-specific T cell therapy
Describe how TCR and CAR T cell therapy works and how these 2 therapies differ
T cells are taken from the patient and vectors are used to insert gene fragents that encode receptors
- In TCR therapy, the gene will encode a specific TCR (e.g. against tumour antigen), but it requires tumour cells to express MHC to be activated
- In CAR therapy, the receptors are chimeric and can be activated by tumour antigens alone
Describe a use of CAR T cell therapy.
Tisagenlecleucel - targets CD19 (present on B cells)
Used to treat ALL and NHL
What is ipilimumab and how does it work?
- Ipilimumab is a monoclonal antibody that blocks CTLA4 (inhibitory T cell receptor)
- Allows for greater T cell activation
- It is used in advance melanoma
Explain the use of antibodies against PD-1 in treating cancer.
- Pembrolizumab and nivolumab are monoclonal antibodies that block PD-1 (inhibitory T cell receptor)
- Prevents tumours expressing PD-L1 from inhibiting T cell response
- Used in advanced melanoma, NSCLC, metastatic renal cell carcinoma
What is the main complication with targetting T cell inhibitory receptors?
Autoimmunity
