Potential therapeutic uses of monoclonal antibodies and cytokines/cytokine antagonists
Clinical uses of immunoglobulin therapy
Understand the use of checkpoint inhibitors in cancer therapy
Understand adoptive cell therapy (T cells, dendritic cells, CAR T cells)
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What gives you
- natural active immunity
- artificial active immunity
- natural passive immunity
- artificial passive immunity
Natural active - exposure to infection
Artificial active - vaccine
Natural passive - placental transfer of IgG and colostral transfer of IgA, immune cells
Artificial passive - Ig therapy, (e.g. rabies Ig), snake bite
Clinical uses of
- Human Normal Immunoglobulin (HNIG)
- Specific immunoglobulins
HNIG used against
-Hep A, measles, polio, rubella
Specific immunoglobulins exist for
-Hep B, rabies, tetanus, VZV
What is IVIg
Plasma derived biologic (from a pool of thousands of donors) for replacement therapy in primary and secondary immunodeficiency disorders
What is IVIg used for
Primary immunodeficiency Idiopathic Thrombocytopenic Purpura (ITP) Myeloma CLL GVHD
Direct types of immunotherapy (i.e. directly damage the tumour cells)
Monoclonal antibodies
Chimeric antigen receptors
(CARs)
Bi-specific antibodies
Indirect types of immunotherapy (i.e. activate immune system to destroy tumour cells)
Tumour vaccines Dendritic cell vaccines Adoptive cell transfer Cytokine therapies Checkpoint inhibitor therapies
How are monoclonal antibodies made
- An antigen is injected into a mouse
- The mouse naturally produces lymphocytes, which produce antibodies specific to the antigen
- Spleen cells which produce the lymphocytes are removed during a small operation
- The spleen cells are fused with human cancerous WBCs called myeloma cells to form hybridoma cells which divide indefinitely
- These hybridoma cells are cultured and divide and produce millions of monoclonal antibodies specific to the original antigen
Checkpoint inhibitors are used for cancers
How do they work?
Immune checkpoints are molecules on certain immune cells that need to be stimulated to start an immune response
When stimulated, it can dampen the immune response to a stimulus.
Some cancer cells can protect themselves from attack by stimulating immune checkpoint targets
So checkpoint inhibitors block inhibitory checkpoints and boost immune response
What is adoptive cell therapy (cellular immunotherapy)
Involves taking out immune cells (usually T cells) from patient and either
-expanding the number of them (i.e. tumor-infiltrating lymphocyte (TIL) therapy) OR
- genetically engineering them equipping them with a new T cell receptor that can target specific cancer antigens (i.e. engineered T cell receptor (TCR) therapy) OR
- equipping the T cells with a synthetic receptor called CAR which can bind to cancer cells even if their antigens aren’t presented on the surface via MHC (i.e. CAR T Cell Therapy)
