Immunotherapy Flashcards
Immune system: Overview
Immune system consists of:
- Physical/chemical barriers
- Specialised immune cells
Role of the immune system: defend the body against threats including microorganisms (bacteria, viruses, fungi) and cancer cells.
T cells: white blood cells that play an important part in the acquired immune response.
The concept of immuno-oncology
- Chemotherapy + tumour-targeted drugs: directly affect the growth and proliferation of tumour cells.
- Immuno-oncological drugs: harness the body’s natural anti-cancer immune response to attack and destroy the cancer.
- Immuno-oncology = manipulation of immune checkpoints
- Immune checkpoints: are designed to turn off the immune response to prevent autoimmunity and damage to healthy cells.
- Checkpoint inhibitors prevent this deactivation and increase the body’s anti-tumour immune response.
Chemotherapy: Overview
Chemotherapy involves the use of one or more drugs to destroy tumour cells, based on the fact that these cells typically divide rapidly.
Side effects are caused by damage to normal cells, especially those that also divide rapidly, such as cells in the bone marrow, hair follicle and GI tract.
Tumour-targeted drugs: Overview
A cancer treatment that uses drugs, but is different from traditional chemotherapy. It works by targeting the cancers specific genes, proteins or the tissue environment that contributes to cancer growth and survival.
Tumour-targeted drugs specifically act against molecular targets in cancer cells identified by tissue and blood samples. These drugs are selected based on the molecular characteristics of the tumour.
Example: Trastuzumab (Herceptin) for HER2 positive cancer
Immunotherapy: Side effect overview
Immune-related side effects arising from treatment with checkpoint inhibitors can affect any organ or tissue, but most commonly affect the:
- Skin
- Colon
- Lungs
- Liver
- Endocrine organs (e.g. thyroid, pituitary)
Side effects: typically appear within a few weeks/months of starting treatment. They can arise up to a year after treatment has finished.
Immunotherapy: Side effect management
- Grade 1 (mild severity)/Grade 2 (moderate severity): managed symptomatically, without interrupting/permanently stopping treatment
- Persistent Grade 2 symptoms : skip one or more treatments (+ receive symptomatic treatment)
- Grade 3 (severe) or Grade 4 (very severe): treatment discontinued + referral to specialist
Immune system
The immune system consists of many different components in the body, some of which act as physical/chemical barriers (skin, cornea, membranes in te respiratory, GI, urinary and reproductive tract) while others make and/or circulate specialised immune cells (the lymphatic system, bone marrow, spleen and thymus gland).
A normal immune system compromises of:
- Recognition of potentially harmful antigens
- Activation and mobilisation of cellular and antibody defences
- Attack against the invader or abnormal cell
- Termination of the attack once the threat has been counteracted.
The immune response consists of 2 phases:
- Innate immunity: quick but not specific
- Acquired immunity: slower but specific
How does the immune system respond to cancer?
- Hiding their identity: a cancer cell can reduce the expression of tumour antigens on its surface, making it more difficult for the immune system to identify it as being normal.
- Putting up a barrier: a cancer cell can express proteins on its surface that inactivate an immune cell.
- Influencing other cells: a cancer cell can influence cells close to it to release substances that suppress the immune response (and facilitate cancer cell proliferation and survival)
Immuno-oncology
Immuno-oncological drugs harness the body’s natural anti-cancer immune response, boosting its ability to attack and destroy the cancer. Immuno-oncological approaches fall into two main cateogories.
- Passive immunotherapy: which facilitates and enhances the body’s existing immune response. Examples include: checkpoint inhibitors.
- Active immunotherapy: which directs the body’s immune cells to recognise, attack and destroy cancer cells. Examples include anti-cancer vaccines.
Immunotherapy: Drug types + examples (4)
- CTLA-4 inhibitors: Ipilimumab
- PD-1 inhibitors (targeting the “lock”): Nivolumab, Pembrolizumab
- PD-L1 inhibitors (targeting the “key”): Atezolizumab, Avelumab, Pembrolizumab, Avelumab, Durvalumab
- Combination therapy: Ipilimumab + nivolumab
Side effects of immunotherapy: Common
- General: fatigue
- Skin: extensive rash/itching
- GI: diarrhoea containing blood/mucus, severe abdo pain
- Endocrine: fatigue, weight loss, nausea/vomiting, excessive thirst/appetite, excessive and/or frequent urination
- Respiratory: shortness of breath, cough
Side effects of immunotherapy: Less common
- Headache
- Confusion
- Muscles weakness or pain
- Numbness
- Painful or swollen joints
- Unexplained fever
- Tendency to bruise easily
- Loss of vision
Immunotherapy: Grading of side effects
- Mild
- Moderate
- Severe
- Very severe
