CANCER VACCINES Flashcards
WHAT ARE CANCER VACCINES AND HOW DO THEY WORK?
- cancer vaccines are immunotherapeutic agents that prevent or treat existing cancers by triggering an immune response to tumour associated antigens.
- they work by enhancing T cell mediated cytotoxicity against cancer cells
WHY ARE CANCER VACCINES NEEDED?
- They help the immune system fight and recognise cancer cells
- they prevent virus related cancers like HPV
- they reduce cancer recurrence
- they provide targeted and less toxic treatment
- they boost the effectiveness of other treatments when combined
DEFINE THE TWO TYPES OF CANCER VACCINES:
- prophylactic (preventative) vaccine - designed to prevent cancers from developing by protecting against viruses that cause cancer, e.g. HPV vaccine prevents against cervical cancer and Hepatitis B vaccine prevents liver cancer
- therapeutic cancer vaccines: used to treat existing cancer, by helping the immune system recognise and destroy cancer cells, inducing tumour specific immune responses. e.g. provenge used for prostate cancer.
5 THERAPEUTIC CANCER VACCINE TYPES:
peptide /protein vaccines
whole tumour cell vaccines
dendritic cell vaccines
nucleic acid based vaccines
viral vector based vaccines
PEPTIDE/PROTEIN VACCINES:
they use small peptides, derived from tumour cells to trigger an immune response.
pros: easy to produce and store, safe, targets specific tumour antigens
cons: HLA restricts, only works for patients with specific HLA types, weak so needs adjuvants for stronger response
NUCLEIC ACID BASED VACCINES (DNA/RNA)
delivers DNA or mRNA that encodes tumour antigens. the body’s cells make the antigen and train the immune system to recognise it.
pros: rapid production, can target multiple antigens, no HLA restriction
cons: risk of degradation, low stability, limited approved cancer uses so fat
DENDRITIC CELL VACCINES:
uses a patients own dendritic cells, then are loaded with tumour antigens and re-infused to activate T cells
pros: highly specific, strong T cell activation, lower risk of attacking normal cells
cons: expensive, time consuming, requires a special lab, effectiveness between patients
WHOLE TUMOUR CELL VACCINES:
Uses killed or modified tumour cells that contain many antigens
pros: broad immune response, personalised if using patients own tumour cells
cons: risk of poor immune activation without boosters, can be hard to grow enough tumour cells, hard to regulate
VIRAL VECTOR VACCINES:
Uses a harmless virus to carry and deliver tumour antigen genes into the body
pros: very strong immune response, deliver genes efficiently into cells, long lasting
cons: risk of immune reaction against the viral vector itself, pre existing immunity to virus can reduce effectiveness
WHAT ARE THE TWO TYPES OF TUMOUR ANTIGENS?
- Tumour-Associated Antigens (TAAs): antigens that are present on both normal and cancer cells, but are abnormally expressed in tumours. E.g. HER2 (breast cancer), CEA (colon cancer), AFP (liver), MAGE-A3 (melanoma, lung)
- Tumour Specific Antigens (TSAs): antigens that are found only on cancer cells, not normal/healthy cells.
they are ideal for targeted therapy as the IS can attack tumours without harming normal cells. E.g. Neoantigens from mutation p53 or Ras gene
what are some challenges in cancer vaccines
- low immunogenicity: some tumour antigens are weakly immunogenic, the immune system may ignore the vaccine and not respond effectively
- tumour heterogeneity: not all cells express the same antigens, so a single vaccine may only target some cells, allowing others to survive and regrow
- immunosuppressive tumour microenvironment (TME): tumours release substances and attract cells like Tregs that suppress immune activation, even if a vaccine triggers a response TME can block it.
- MHC downregulation: some cancer cells lose MHC molecules which are needed to present antigens to CD8+ T cells. This allows tumour to hide from the immune system, vaccine is then less effective
STRATEGIES TO IMPROVE CANCER VACCINES:
- Combination with immune checkpoint inhibitors: these help overcome immune suppression by removing inhibitors on T cells allowing them to attack cancer cells more effectively
- using strong adjuvants: they enhance the body’s immune response to the target antigen
- combine with other therapies such as chemotherapy, radiation or CAR-T cells to enhance overall response
DISCUSS TWO MAJOR VACCINE S WHICH HAVE BEEN APPROVED FOR THE PREVENTION OF HUMAN CANCERS:
HPV vaccine and Sipuleucel-T (provenge).
HPV Vaccine e.g. Gardasil and Cervarix, is a preventative vaccine designed to protect against infection by high risk types of the human papillomavirus especially types 16 and 18, which are linked to cervical, anal and oropharyngeal cancers. its most effective when administered before the individuals become sexually active.
Sipuleucel-T is a therapeutic agent approved for the treatment of metastatic prostate cancer in men with minimal symptoms, its a type of dendritic cell vaccine where a patients immune cells are collected and activated outside the body using prostate cancer antigen (PAP), then reinfused to stimulate the body’s immune system to attack the cancer.
DISCUSS TWO OTHER APPROVED VACCINES:
Hepatitis B virus vaccine (HBV) and Bacillus calmette-geurin vaccine (BCG)
HBV vaccine is a preventative vaccine that protects against infection with the hepatitis B virus, a major risk factor for hepatocellular carcinoma (liver cancer). chronic HBV infection leads to ongoing liver inflammation, cirrhosis, eventually liver cancer. by preventing HBV infection, the vaccine indirectly reduces incidence of liver cancer. its administered in infancy.
BCG vaccine, originally developed as a vaccine for tuberculosis, also approved as therapeutic cancer vaccine for non muscle invasive bladder cancer (NMIBC). it is administered directly into the bladder, where it stimulates a localised immune response that targets and destroys bladder cancer cells.
DISCUSS THE ‘IMMUNE SURVEILLANCE CONCEPT’ AND PROVIDE EVIDENCE IN SUPPORT OF THIS CONCEPT.
The immune surveillance concept proposes that the immune system plays a critical role in detecting and destroying emerging tumour cells, before they develop into clinically detectable cancers. one evidence is the presence of tumour infiltrating lymphocytes (TILs) in human tumours. E.g. there are high levels of CD8+ T cells in cancers like melanoma or colorectal cancers. this shows the immune system is actively recognising and attacking tumours. Another example is immunocompromised patients have higher cancer risk, e.g. organ transplant patients on immunosuppressants or HIV/AIDS patients, they develop cancer more frequently, showing the immune system normally suppresses tumour development.
WHAT ARE FIVE MECHANISMS BY WHICH TUMOURS ESCAPE IMMUNE RECOGNITION AND DESTRUCTION?
- Downregulation of MHC class I molecules: Tumours may reduce or lose expression of MHC I, which is essential for presenting antigens to CD8+ cytotoxic T cells, helping them evade immune detection.
- secretion of immunosuppressive cytokines: tumour cells can secrete cytokine like TGF-B, IL-10 which suppress T cell activation and promote immunosuppressive tumour microenvironment.
- recruitment of immunosuppressive cells: tumours attract cells like Tregs and MDSC’s that inhibit anti tumour immune responses
- expression of immune checkpoint ligands: tumours express proteins such as PD-L1, which bind to PD1-receptors on T cells, inhibiting their function and leading to T cell exhaustion
- antigen loss variants: tumour cells may undergo genetic changes to stop expressing specific tumour antigens, making them invisble to antigen specific T cells
DISCUSS APPROACHES TO DEVELOPING CANCER VACCINES
Cancer vaccine development involves multiple strategies aimed at stimulating the immune system to recognize and eliminate cancer cells. These approaches can be broadly divided into preventive and therapeutic vaccines
- Peptide-Based Vaccines
- nucleic acid based vaccines
- dendritic cell vaccine
- whole tumour cell vaccine
- viral vector based vaccines
USING SPECIFIC EXAMPLES, DISCUSS VARIOUS IMMUNOTHERAPEUTIC STRATEGIES, WHICH HAVE BEEN APPROVED FOR USE IN THE TREATMENT AND PREVENTION OF HUMAN CANCERS.
immunotherapy aims to enhance the bodsys immune system to fight cancer, the strategies that have been approved, include:
- immune checkpoint inhibitors: these drugs block inhibitory receptors on T cells, restoring their ability to attack cancer cells e.g. ipilimumab is approved for melanoma by blocking CTLA-4 OR PD-1 pathways.
- cancer vaccines: stimulate the immune system to recognise and attack tumour specific antigens. e.g. preventative vaccines or therapeutic vaccines
- adoptive cell therapy (ACT): Involves modifying or expanding a patient’s immune cells and reinfusing them to attack tumours. e.g CAR-T cell therapy.
- monoclonal antibodies: these lab made antibodies bind specific antigens on cancer cells and mediate immune responses like antibody dependent cell mediated cytotoxicity. e.g Trastuzuman targets HER2 in HER2 positve breast cancer.
- cytokine therapy: cytokines enhance immune systems ability to target tumours. e.g. interleukin-2 used in renal cell carcinoma and melanoma, but its high toxicity limits use.
PROVIDING SPECIFIC EXAMPLES, DISCUSS FOUR TYPES OF TUMOUR ANTIGENS THAT ARE RECOGNISED BY CD8+ T CELLS.
CD8+ T cells recognise tumour antigens presented MHC class I molecules, these antigens may be classified in the types:
- tumour specific antigens (TSAs)/Neoantigens: these are derived from mutations unique to tumour cells, not found on normal cells. cells E.G. Mutated KRAS or EGFR peptide in lung cancer. antigens are present only on cancer cells. they are ideal for targeted therapy as the immune system can attack the tumours without harming the normal cells
- tumour associated antigens (TAAs): These are overexpressed or aberrantly expressed self-antigens found in tumours and sometimes in normal tissue at low levels. Are present on both the healthy cells and cancer cells but are abnormally or overexpressed on tumour . E.G. HER2 in breast cancer, CEA in colon cancer
- cancer testis antigen: these are normally only expressed in immune-privileged sites like the testis, but are aberrantly expressed in various cancers. E.g. MAGE-A3, NY-ESO-1.
- viral antigens: In virus-induced cancers, viral proteins act as tumour antigens. E.g. E6 and E7 proteins from high risk HPV types in cervical cancer.
