10 immunotherapy Flashcards
What diseases have been eradicated due to vaccination?
Smallpox has been eradicated; polio is close to eradication.
What are newer vaccine development approaches?
mRNA vaccines, DNA vaccines.
Name two prophylactic cancer vaccines
HPV vaccine, HBV vaccine.
How does the HPV vaccine work?
Contains recombinant virus-like particles with L1 capsid antigen, inducing strong neutralising antibody response.
What age group in the UK receives the HPV vaccine?
Girls aged 12-13 since 2008.
What is the main purpose of the Hepatitis B vaccine?
Prevent chronic HBV infection and reduce the risk of hepatocellular carcinoma.
Name the first FDA-approved cancer treatment vaccine.
Sipuleucel-T (Provenge®) for metastatic prostate cancer.
How is the BCG vaccine used in cancer therapy?
Used to treat bladder cancer by inducing necrosis and cytokine release.
What is an adjuvant?
A substance that enhances the body’s immune response to an antigen.
Name an example of an adjuvant used in vaccines.
Aluminium salts (Alum).
Why are adjuvants necessary in some vaccines?
To enhance immune response, especially in non-live vaccines.
What is desensitisation used for?
Treating allergies through controlled exposure to allergens.
What immunological shift does desensitisation cause?
Switch from IgE to IgG4, promoting Treg response.
What are possible side effects of desensitisation?
Anaphylaxis, local reactions.
What are cytokines?
Small proteins that mediate immune responses.
Name a cytokine used in therapy and its function.
G-CSF; stimulates neutrophil production.
What is a major side effect of G-CSF therapy?
Bone pain.
What does Pembrolizumab (Keytruda) target?
PD-1 receptor on T cells.
How does Pembrolizumab work?
Blocks PD-1 to reactivate T cells against tumour cells expressing PD-L1.
What is the risk of Pembrolizumab therapy?
It may cause autoimmune reactions.
Name a monoclonal antibody used for kidney transplant rejection.
Basiliximab (CD25 targeting IL-2 receptor alpha).
What is the function of TNF-alpha?
Pro-inflammatory cytokine involved in immune responses.
How can TNF-alpha be inhibited?
Using infliximab (TNF-alpha inhibitor), useful in RA and Crohn’s disease.
What is IVIG therapy?
Intravenous immunoglobulin therapy; provides passive immunity in antibody-deficient individuals.
What type of immunoglobulin is used in IVIG?
IgG only.
What is HSCT and what is it used for?
Haematopoietic stem cell transplantation, used for SCID, leukaemia, and metabolic disorders.
What are the sources of HSCT?
Peripheral blood, bone marrow, foetal cord blood.
What is the difference between autologous and allogeneic HSCT?
Autologous: patient’s own cells; Allogeneic: donor cells.
What is gene therapy?
Replacement of defective genes with normal genes in stem cells.
Name a gene therapy licensed in Europe for ADA-SCID.
Strimvelis (2016).
What is the mechanism of ADA-SCID gene therapy?
Introduces functional ADA enzyme to allow lymphocyte development.
Which vaccines prevent cancer?
HPV, HBV.
What strains of HPV are in Gardasil?
HPV 6, 11, 16, 18.
What immune response protects against HPV?
Neutralising antibodies.
Which vaccine treats bladder cancer?
BCG vaccine.
Define an adjuvant.
Enhances immune response to antigen.
What is in Freund’s complete adjuvant, and is it licensed in humans?
Includes BCG, banned due to toxicity.
How do adjuvants work?
Activate innate immunity, enhance adaptive response.
What are the steps in desensitisation?
Increasing allergen doses over time.
What adverse reaction can occur during desensitisation?
Anaphylaxis.
What is G-CSF and its importance?
Stimulates neutrophil production.
What do antibodies do?
Bind antigens, mediate immune responses.
Which monoclonal antibody type is most immunogenic?
Fully mouse.
What does OKT3 bind to and its effect?
CD3, depletes T cells.
When is OKT3 used clinically?
Acute transplant rejection.
What is the target of Basiliximab?
CD25, IL-2 receptor alpha.
What does TNF-alpha do?
Mediates inflammation.
How can TNF-alpha effects be reduced?
Anti-TNF drugs like infliximab.
How does Keytruda work?
Blocks PD-1 to enhance T cell response against cancer.
What is the function of T regulatory cells in desensitisation?
Suppress excessive immune responses.
What are the limitations of prophylactic cancer vaccines?
Limited efficacy against established tumours.
Mainly effective in preventing tumour development.
Requires identification of tumour-specific antigens.
How do tumour-specific antigens help in cancer vaccines?
They are unique to tumour cells.
Can be viral-derived (e.g., HPV, HBV).
Stimulate immune responses targeting cancer cells.
How does BCG therapy work for bladder cancer?
Induces necrosis in tumour cells.
Triggers cytokine release (IL-1, IL-6, TNF-α).
Activates CD8+ T cells via tumour antigen presentation.
What is MF-59 and how does it work?
A squalene-based adjuvant used in Europe.
Enhances antigen uptake by APCs.
Promotes a strong immune response.
Why are bacterial components used as adjuvants?
Mimic natural infection patterns.
Activate TLR/NOD-like receptors on APCs.
Enhance adaptive immune response.
What is the primary goal of desensitisation therapy?
Reduce allergic sensitivity to specific allergens.
Shift immune response from Th2 (IgE) to Th1/IgG4.
Reduce mast cell and basophil activation.
Why are regulatory T cells (Tregs) important in desensitisation?
Suppress allergic inflammation.
Modulate immune response to allergens.
Express CD25+ and produce IL-10, TGF-β.
What is the role of IL-21 in immune response?
Produced by T follicular helper (Tfh) cells.
Essential for B cell activation and antibody production.
Enhances CD8+ T cell responses.
Why is TGF-β important in immune regulation?
Suppresses excessive immune activation.
Essential for Treg function.
Involved in wound healing and tissue repair.
How does antibody-dependent cellular cytotoxicity (ADCC) work?
Antibody binds to antigen on target cell.
Fc region engages NK cells via Fcγ receptors.
NK cells release perforins and granzymes to kill target.
What are the risks of monoclonal antibody therapy?
Immune-related adverse effects (e.g., autoimmunity).
Infusion reactions (fever, chills, anaphylaxis).
Opportunistic infections due to immune suppression.
How is immunoglobulin replacement therapy administered?
Intravenous (IVIG) or subcutaneous (SCIG).
Given every 2-3 weeks.
Derived from pooled donor plasma (IgG only).
What are the advantages of autologous HSCT over allogeneic HSCT?
Lower risk of graft-versus-host disease (GvHD).
No need for a matched donor.
Reduced risk of immune rejection.
Why do allogeneic HSCT patients need immunosuppression?
Prevents rejection of donor cells.
Minimises graft-versus-host disease (GvHD).
Requires careful monitoring for infections.
. Why was Glybera withdrawn from the market?
High cost (~$1 million per treatment).
Limited clinical demand.
Complex regulatory and logistical challenges.
How does Strimvelis treat ADA-SCID?
Uses a retroviral vector to insert a functional ADA gene.
Modified stem cells reinfused into the patient.
Restores lymphocyte development and function.
What are the steps in developing a prophylactic cancer vaccine?
- Identify Tumour-Specific or Viral Antigens
E.g., HPV (cervical cancer), HBV (liver cancer). - Produce Recombinant Antigen
Express in yeast (e.g., Saccharomyces cerevisiae for HPV/HBV vaccines). - Formulate with Adjuvant
Enhances immune response. - Administer Vaccine
Typically 2-3 doses over months. - Induce Immune Response
APCs present antigen to T/B cells.
Generates memory T/B cells and neutralising antibodies.
How does the BCG vaccine treat bladder cancer?
B1. CG is Instilled Directly into the Bladder
Unlike systemic vaccines, it is applied locally.
- BCG Uptake by Urothelial Cells
Some tumour cells internalise the bacteria. - Activation of Innate Immune Response
BCG stimulates macrophages and dendritic cells. - Cytokine Release (IL-1, IL-6, TNF-α)
Triggers a strong Th1 immune response. - CD8+ T Cells Become Activated
Recognise tumour antigens and kill tumour cells. - Long-Term Immunity & Recurrence Prevention
Some patients develop long-lasting protection.
How do adjuvants enhance vaccine effectiveness?
- Vaccine Administered with Adjuvant
Adjuvant included to enhance immune response. - Innate Immune System Activation
Triggers pattern recognition receptors (TLRs, NOD-like receptors). - Recruitment of APCs (Dendritic Cells, Macrophages)
Increased antigen uptake and presentation. - Cytokine Release & Inflammation
Promotes stronger immune activation. - Enhanced Adaptive Immune Response
More efficient T and B cell activation. - Long-Lasting Immunity Developed
Adjuvants can prolong antigen exposure.
What are the steps in desensitisation for allergies?
- Identify the Specific Allergen
Common allergens: pollen, insect venom, dust mites. - Gradual Exposure to Small Allergen Doses
Weekly injections or sublingual tablets. - Increase Allergen Dose Over Time
Usually over 14-18 weeks. - Induce Immune Tolerance
Switch from Th2 (IgE-mediated) to Th1/IgG4 response. - Regulatory T Cells (Tregs) Suppress Allergy Response
Produce IL-10 and TGF-β to control inflammation. - Long-Term Immune Tolerance Maintained
Requires regular maintenance doses.
How does Pembrolizumab (anti-PD1 therapy) work?
- PD-1 Receptor on T Cells Detects PD-L1 on Tumour Cells
- Normally, this “off switch” prevents T cells from attacking. - Cancer Cells Overexpress PD-L1
- Helps them evade immune detection. - Pembrolizumab Blocks PD-1 from Binding to PD-L1
- Removes the immune suppression. - T Cells Recognise Tumour Cells as Foreign
- Increased cytotoxic T cell activation. - Tumour Cells Are Attacked & Destroyed
- Immune system effectively combats cancer. - Potential Autoimmune Side Effects
- Due to broad immune activation, normal cells may be attacked.
How does G-CSF therapy stimulate neutrophil production?
- Patient Receives Recombinant G-CSF (Filgrastim/Neupogen)
- Given subcutaneously or intravenously. - Binds to G-CSF Receptors on Bone Marrow Stem Cells
- Stimulates differentiation of haematopoietic stem cells. - Increases Neutrophil Production & Release into Bloodstream
- Reduces risk of infections in neutropenic patients. - Mobilises Haematopoietic Stem Cells
- Used for stem cell transplantation. - Potential Side Effects
- Bone pain, allergic reactions, splenomegaly.
What are the steps in monoclonal antibody therapy?
- Identify Target Antigen (e.g., CD20, PD-1, HER2)
Specific to disease (e.g., Rituximab for CD20+ B cells in lymphoma). - Generate Antibodies in a Host System
Hybridoma technology or recombinant production. - Modify Antibody (Humanised, Chimeric, Fully Human)
Reduces immune rejection. - Administer Antibody to Patient
Intravenous or subcutaneous infusion. - mAb Binds to Target Cells
Can block signalling, induce cell death, or recruit immune response. - Clearance of Diseased Cells
Via ADCC, complement activation, or direct apoptosis. - Monitor for Side Effects
Infusion reactions, autoimmune effects, cytokine storm.
How does gene therapy work for ADA-SCID?
- Extract Haematopoietic Stem Cells (HSCs) from Patient
Typically from bone marrow or peripheral blood. - Use a Viral Vector to Insert a Functional ADA Gene
Usually a retrovirus or lentivirus. - Transduce Stem Cells with the ADA Gene
Modified cells now express functional adenosine deaminase. - Reintroduce Corrected Stem Cells into Patient
Via intravenous infusion. - Stem Cells Repopulate Bone Marrow
Generate functioning T/B cells. - Monitor for Immune Restoration & Potential Risks
Risk of insertional mutagenesis (leukaemia development).
How does IVIG therapy work for immunodeficiencies?
- Plasma from Thousands of Donors is Collected
Provides a broad range of antibodies. - IgG is Purified & Tested for Safety
- Removes pathogens and contaminants. - Administered via Intravenous Infusion
- Typically every 2-3 weeks. - Antibodies Provide Passive Immunity
- Immediate protection against infections. - Regular Monitoring for Efficacy & Side Effects
- Side effects: headache, fever, allergic reactions.
