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Immunological Mechanisms Of Clinical Responsiveness To Immunotherapy For Metastatic Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$480,750.00
Summary
There have been no major improvements in the treatment of most metastasizing, solid tumours in the last several decades. One avenue that has received much attention is boosting a cancer patient's immune system with an anti-cancer vaccine, so that it destroys just the cancerous cells. This has proved an elusive goal, and no treatment has ever been shown to be of repeated worth, in the complete resolution of multiple sites of metastatic disease, until now. Two consecutive trials of our dendritic c ....There have been no major improvements in the treatment of most metastasizing, solid tumours in the last several decades. One avenue that has received much attention is boosting a cancer patient's immune system with an anti-cancer vaccine, so that it destroys just the cancerous cells. This has proved an elusive goal, and no treatment has ever been shown to be of repeated worth, in the complete resolution of multiple sites of metastatic disease, until now. Two consecutive trials of our dendritic cell based vaccine, which uses only cells from the patient to be treated, have each shown a 15% complete, durable, response rate. The remissions have now lasted longer than 3 years in patients otherwise expected to survive less than 1 year, with no serious side effects observed in any of the patients treated. It is likely that part of the success of this treatment is that it targets unique mutations in the patient's own cancer cells, in combination with a powerful immune stimulation from the dendritic cells. In contrast, most carefully run trials, now and in the recent past, have attempted to use more generic targets, common to many patients' cancers. The problem with this approach is likely to be that the patient is tolerant to these, since the targets are common, self proteins. At variance with all previous trials, we found an exact correlation between durable clinical responses and the degree of anti-tumour immunity displayed by the patients T cells. This grant proposal is based on the reasoning that, by studying in depth the characteristics of this successful immune response, in patients with complete, durable, clinical responses, we will be able to make major improvements in the formulation of the therapy.Read moreRead less
Cancers have been found to contain 'stem cells' which are responsible for tumours growing and spreading throughout the body. Cancer therapies often target the cancer, but it is now clear the these treatments will only be effective if they can eradicate the malignant stem cells. This research investigates the best way of 'targeting' cancer stem cells in malignant melanoma as a means of developing more effective anti-cancer treatments.