Immunotherapy With Checkpoint Blocking Antibodies Case Study

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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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(2010) report a significantly increased median overall survival in patients with melanoma treated with ipilimumab (a CTLA-4 blocking antibody), compared to those receiving a glycoprotein peptide vaccine (gp100) which has been shown to induce immune responses but has limited anti-tumour activity (Rosenberg et al., 2004), as an active control. This study provides evidence supporting the effectiveness of a CTLA-4 blocking antibody (in terms of survival rate), which is the reason for the analysis of this study. 676 patients with previously (unsuccessfully) treated metastatic melanoma were randomly assigned to receive ipilimumab plus gp100, ipilimumab alone, or gp100 alone. Ipilimumab treatment was given every three weeks at a dosage of 3 mg/kg, for up to 12 weeks. The median overall survival in the ipilimumab plus gp-100 treatment group was 10.0 months (95% CI 8.5 – 11.5), compared to 6.4 months (95% CI 5.5 – 8.7) in the gp-100 only treatment group, and 10.1 months (95% CI 8.0 – 13.8) in the ipilimumab only treatment group. A statistically significant increase in median survival time was found in the ipilimumab plus gp-100 treatment group compared to the gp-100 only treatment group (p0.05). Another key finding was that when mice that had completely rejected the tumour were re-inoculated, 93 % of the combination group were completely resistant to tumour re-challenge. The study could have been expanded by experimenting with a range of doses of each of the …show more content…
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