Case Study: Immunotherapy With Checkpoint-Blockinging Antibodies

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Question 2
Immunotherapy with checkpoint blocking antibodies: A new novel strategy in cancer treatment
In addition to conventional methods of cancer treatment, the body’s own immune system can have activity against cancer. It was first hypothesised that some cancers can be recognised by the immune system, a concept known as “immune surveillance” (Burnet, 1970). Studies in animal models have provided support for the idea that pre-established immunity to tumour associated antigens can result in increased survival (Eddy et al., 1964). Of more recent interest for therapeutic purposes are antibodies which act to increase the activity of T cells (immune cells which kill cells displaying a specific antigen by binding and releasing cytotoxic chemicals)
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Two such modulators are the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death receptor-1 (PD-1), which are expressed as receptors on the surface of T cells and negatively regulate the T cell response. It has been shown that some tumour cells can express the ligand for the PD-1 receptor, actively preventing the T cells from acting against the tumour (Zou and Chen, 2008). Therapeutically blocking CTLA-4 and PD-1 using antibodies decreases the negative regulation of T cells and can therefore allow a greater T cell response against cancer (Callahan and Wolchok, 2013). Several therapeutics of this type are currently approved to treat metastatic melanoma (Kyi and Postow, 2013). The use of antibodies which target CTLA-4 and PD-1 as cancer therapeutics has gained significant attention in recent years as a novel and effective strategy to treat cancer, and will be discussed in the context of recent literature. Four recent studies which highlight improved survival in advanced melanoma treated with PD-1 and CTLA-4 blocking …show more content…
Not only do the above studies allow us to conclude that treatment with ipilimumab and nivolumab shows effectiveness against advanced melanoma, but also that it can have a synergistic effect when combined with conventional chemotherapy. The duration of response and immunological memory effects reported in some of the studies are particularly

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