3.3 Large Molecules, Monoclonal antibodies

Question 1

What is a monoclonal antibody?

Answer 1

A “y” shaped protein that binds to a specific antigen on cancer cells

Note it can also bind to fungi, viruses, bacteria

Question 2

What are 4 ways monoclonal antibodies are produced?

Answer 2

Monoclonal antibodies are copies of antibodies mass produced in a laboratory from either a:

• Murine source
• Chimeric source
• Humanised source
• Fully Human source

Question 3

What is the suffix for a monoclonal antibody?

Answer 3

Mab

Question 4

A number of monoclonal antibodies have lost their period of marketing exclusivity, what opportunity does this present for the NHS to save money.

Answer 4

• When an originator biotech company launches a monoclonal for the first time they are granted a period of marketing exclusivity when no other company can copy their drug
• Once this period of marketing exclusivity expires, other companies can produce competitor biosimilar products which are given the same license and are significantly less expensive.

Question 5

A biosimilar medicine …

Answer 5

• has exactly the same active ingredient as the original drug
• Is highly similar to the original biological product

Question 6

What are the 2 ways monoclonal antibodies exert their anti cancer effect?

Answer 6

Direct mechanisms
indirect mechanisms

Question 7

What are the two direct mechanisms by which monoclonal antibodies exert their effect?

Answer 7

MABs bind with a target receptor, or protein on the cell

• This blocks those signals required for cell growth and survival.
• e.g. Cetuximab

MABs may be combined with other agents such as cytotoxic drugs, radioisotopes or cytokines

• This facilitates the direct delivery of a toxic substance into the cell
• e.g. Trastuzumab emtansine

Question 8

What are 5 indirect mechanisms by which monoclonal antibodies exert their effect?

Answer 8

Indirect mechanisms may bind directly to specific antigens on targeted cells, flagging them for destruction by immune cells.

This may be induced by the following mechanisms:

Antibody-dependent cellular cytotoxicity (ADCC)
* involves the activation of natural killer cells, macrophages and neutrophils resulting in cell lysis and phagocytosis respectively.

Complement-dependent cytotoxicity (CDC)
* CDC involves the activation of molecules to release cytokines that attack cellular membranes resulting in cell death.

Antibody-dependent cellular phagocytosis (ADCP)
* ADCP involves the engagement of macrophages and other phagocytes to ingest cancer cells.

Immune checkpoint blockade
* This involves interruption of immunosuppressive extracellular signalling.

Binding and delivery
* Binding and delivery of the target cancer cells to the proximity of immune effector cells in order to enable immune-mediated tumour cell killing (e.g. bispecific T-cell engager (BiTE) MABs such as blinatumomab).