Posted by: Sophie Khatib20 DEC 2012
I have been doing a lot of reading this evening (mainly because I have got a piece of work that needs doing and I am trying to put it off!!). I am really interested in antibodies and my mind started to wander – what else could they be used for?
There’s a lot of research at the minute trying to develop antibodies with drug molecules attached to it via a linker molecule. This research is mainly being done with the idea to develop targeted cancer treatments to deliver highly cytotoxic molecules directly to a cancer cell, increasing its specificity which not only reduces side effects but increases the efficacy of the drug.
Antibodies can be used to accurately deliver a drug to a cancer cell, taking advantage of the fact that cancers cells commonly express a unique antigen on their surface. Once antibodies, which recognise this antigen have been developed, drug molecules can be attached. It is believed that these antibody-drug complexes work because they are incorporated into the target cell and lysosomal enzymes can cleave the drug molecule from the complex. This idea is particularly important because it means the complex is inactive, i.e. the drug molecule will not have its effect anywhere while it is still attached to the antibody. It is when the drug molecule is cleaved off that it effectively becomes an active drug and can exert its cytotoxicity.
This is all well and good but there needs to be the right drug in place, specific to each type of cancer and modified multiple times according to different patients.
One of the problems with traditional chemotherapy is its well established and problematic side effects of immunosuppression. But as I mentioned in a previous blog, the immune system actually has cells that are capable of attacking cancer cells when in the bloodstream. So, why can’t we use the immune system and its cells and help our body fight off disease rather than suppressing it?!
In an ideal situation, in my head anyway, we could attach natural killer (NK) cells to an antibody and deliver our own immune system to the place it is needed, direct to the cancer. This way, there would be little variation between cancer treatments as it would only need to be the antibody that is changed to recognise different cancers, rather than the antibody AND the drug molecule. Also, there would be the huge advantage of minimal side effects – although the drug-antibody complexes are specific, there is still the chance that the cytotoxic anticancer agent will be released in the wrong place or be cleaved off too early and so may be circulating round the body, causing problems, but this would be greatly reduced if we are using our own immune cells
Natural killer cells have the huge advantage of being host derived – it is something you normally produce, we would just need more of them. NK cells are lymphocytes with no immunological memory, normally produced by the innate immune system. They exert their action by producing pores in the target call membrane and inducing apoptosis while cleaving the host cell’s DNA. This is the way in which the majority of cancer cells in the bloodstream are destroyed, as only a very small percentage of migrating cancer cells actually grow and form a metastatic tumour. This implies that it is a highly successful model in the majority of instances. Now that is an exciting idea, is it not?