6 - immunotherapy

Question 1

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)

Answer 1

.

Question 2

What gives you

• natural active immunity
• artificial active immunity
• natural passive immunity
• artificial passive immunity

Answer 2

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

Question 3

Clinical uses of

• Human Normal Immunoglobulin (HNIG)
• Specific immunoglobulins

Answer 3

HNIG used against
-Hep A, measles, polio, rubella

Specific immunoglobulins exist for
-Hep B, rabies, tetanus, VZV

Question 4

What is IVIg

Answer 4

Plasma derived biologic (from a pool of thousands of donors) for replacement therapy in primary and secondary immunodeficiency disorders

Question 5

What is IVIg used for

Answer 5

Primary immunodeficiency
Idiopathic Thrombocytopenic Purpura (ITP)
Myeloma
CLL
GVHD

Question 6

Direct types of immunotherapy (i.e. directly damage the tumour cells)

Answer 6

Monoclonal antibodies
Chimeric antigen receptors
(CARs)
Bi-specific antibodies

Question 7

Indirect types of immunotherapy (i.e. activate immune system to destroy tumour cells)

Answer 7

Tumour vaccines
Dendritic cell vaccines
Adoptive cell transfer
Cytokine therapies
Checkpoint inhibitor therapies

Question 8

How are monoclonal antibodies made

Answer 8

1. An antigen is injected into a mouse
2. The mouse naturally produces lymphocytes, which produce antibodies specific to the antigen
3. Spleen cells which produce the lymphocytes are removed during a small operation
4. The spleen cells are fused with human cancerous WBCs called myeloma cells to form hybridoma cells which divide indefinitely
5. These hybridoma cells are cultured and divide and produce millions of monoclonal antibodies specific to the original antigen

Question 9

Checkpoint inhibitors are used for cancers

How do they work?

Answer 9

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

Question 10

What is adoptive cell therapy (cellular immunotherapy)

Answer 10

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)