Early diagnosis of melanoma remains extremely challenging. Currently there are no validated blood-based biomarkers for early diagnosis. Therefore, a reliable screening test is an unmet medical need. Autoantibodies are emerging as promising biomarkers for early cancer detection. In a proof of principle experiment we identified five autoantibodies that provide 95% sensitivity / specificity. Now we will confirm and validate our findings and develop a clinical test for melanoma diagnosis.
CARPETS: A Phase I Open Label Study Of The Safety And Immune Effects Of An Escalating Dose Of Autologous GD2 Chimeric Antigen Receptor-Expressing Peripheral Blood T Cells In Patients With Metastatic BRAF-Mutant And GD2-Positive Melanoma
Funder
National Health and Medical Research Council
Funding Amount
$351,583.00
Summary
Malignant melanoma is increasing in incidence in Australia. Current drugs for advanced melanoma are only sometimes effective. BRAF blocking drugs with promising anti-melanoma activity are being tested in Australia but drug resistance is developing. We will genetically engineer the patient’s own T cells to redirect them against the melanoma. The feasibility, safety, and immune effects of this approach will be tested in patients whose advanced melanoma is no longer responding to BRAF blockers.
IMMUNOTHERAPY OF MELANOMA WITH DENDRITIC CELL VACCINES
Funder
National Health and Medical Research Council
Funding Amount
$496,980.00
Summary
Melanoma is a skin cancer which continues to increase in incidence in Australia. It is a significant cause of morbidity and mortality because of its tendency to spread from skin to other body sites. It is largely resistant to chemotherapy. Immunological approaches to its treatment hold promise but there is a need to develop more effective vaccines to assist in treatment. Preliminary studies suggest that injection of dendritic cells primed with melanoma antigens induce strong immune responses and ....Melanoma is a skin cancer which continues to increase in incidence in Australia. It is a significant cause of morbidity and mortality because of its tendency to spread from skin to other body sites. It is largely resistant to chemotherapy. Immunological approaches to its treatment hold promise but there is a need to develop more effective vaccines to assist in treatment. Preliminary studies suggest that injection of dendritic cells primed with melanoma antigens induce strong immune responses and regression of melanoma. If this can be confirmed it will represent a significant advance in treatment of the disease. The studies in the proposal are to investigate whether a new form of treatment based on immunisation with dendritic cells sensitised with tumour antigens will prove to be more effective than existing treatments. Dendritic cells are responsible for stimulating immune responses and are grown from the patient's blood. They are then sensitised with tumour antigens and injected into the lymph nodes of the patient. The study will also measure immune responses during the immunisation procedure and assess whether these measures can predict clinical responses in the patient. If the study is successful in its objectives it will assist in development of more effective treatment of melanoma.Read moreRead less
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