Recognition of self and non-self

Through the rearrangement and mutation of genes, T cells collectively produce millions of unique receptors that recognise a huge range of antigens. Each individual T cell produces many copies of a single but genetically unique receptor. During T cell development in the thymus, cells are checked to ensure that they do not strongly recognise peptides derived from the body’s own proteins (self-proteins); cells that do so are deleted. As development of an antibody response requires T cells, this system also prevents the production of strongly self-reactive antibodies. 

However, for a successful immune response against cancer, the body’s own cells must be targeted and destroyed. In the anti-infection immune response, T cells recognise peptides derived from pathogens relatively easily, as they are very different from peptides derived from self-proteins. However, as cancer cells are very similar to healthy cells, recognition and elimination is much more difficult. The development of anticancer T cell therapies has therefore been immensely challenging and the process has been hindered by difficulties in identifying targets that are cancer specific and expressed on all cells of a tumour. Moreover, finding targets that are shared across patients with the same disease has been even harder and has been a major barrier to developing scaleable, economically viable treatments.

Nevertheless, antibodies have been developed as very successful anticancer drugs. These antibodies target intact proteins that are expressed on the surface of cancer cells and are often shared across cancers. However, they are often not specific to cancer cells and do not generally kill cancer cells directly. Therefore, they have a deleterious effect on healthy cells and because of indirect killing, their potency is much less than that of a T cell. As such, antibody treatments are rarely a cure on their own and their use is complicated by allergic reactions and the requirement for repeated doses.