New research findings showcased at the 13th European Cancer Conference (ECCO) have highlighted the important therapeutic potential of immunotherapy in the treatment of a number of different cancers e.g. for treatment of renal and skin cancers.
Renal cancer is the 6th leading cause of cancer death with a survival rate of 11% for stage-IV disease. More than a million skin cancer cases occur each year globally, with a 5-year survival rate of 7 to 9% and a 10-year survival rate of 3 to 6% for stage IV melanoma. These cancers are associated with significant mortality for which survival statistics have remained essentially unchanged for several decades. Past studies have indicated vaccination as a route to boosting anti-tumour T-cell reponses to help kill malignant cells. US investigator Dr Arkadiusz Dudek, from the University of Minnesota, and his team have developed a new method of vaccine-induced augmentation of tumour specific cytotoxic T-lymphocyte responses with the use of latex or silica beads.
The new large multivalent immunogen (LMI) was trialed in 61 patients with renal cancer or malignant melanoma with positive results.
In renal cancer patients, the LMI vaccine was found to prolong time to disease progression to 12.2 months. A significant increase when compared to the standard therapy of renal cancer (high dose interleukin-2) which produced a median progression-free survival of 3.1 months1. Using indicators of median overall survival, patients treated with high dose interleukin-2 survived 17.5 months1 and those treated with the LMI vaccine survived longer than 17.04 months and at current follow up, more than 19 months.
"Our study findings offer hope for patients with metastastic renal cell carcinoma, as this therapy stabilises and controls disease for an average of one year. For patients with metastastic malignant melanoma a large multivalent immunogen vaccine strategy needs to be optimised in order to obtain reproducible results. We hope that by utilising an allogeneic (using human donor cells/tissue) strategy we will observe more frequent and longer lasting responses. This vaccine strategy has no toxicities and treatment is convenient for patients as the vaccine is administered only once a month. In contrast, standard therapeutic strategy using high dose interleukin-2 is very toxic and limited only to selected patients with good performance status, and no cardiac or pulmonary co-morbidities," noted Dr Dudek.
Another immunotherapeutic approach which seeks to boost the responses of effector CD8+ T-cells are DEX vaccines; Dendritic cell derived-EXosomes. In results presented at ECCO, the DEX vaccine, in combination with the alkylating agent cyclophosphamide (CTX), was found to produce antitumour effects superior to that obtained with either the peptide Gp100 plus CTX, or the best DEX vaccination approach currently available in a mouse model of melanoma.
In this new immunotherapeutic approach, CTX acts synergistically with DEX to abolish the function of Treg cells -- cells induced by the tumour which suppress the CD8+ responses evoked by DEX. By abrogating the suppressive effect of Treg, CTX maximises the curative effects of DEX vaccination. The success of this combination approach suggests that future therapeutic vaccines aimed at boosting tumour-primed effector T-cells may benefit from procedures that minimise the pro-tumour effects of Treg cells.
About Renal Cancer
Renal cancer is defined as malignancy of the kidney, the organ that is primarily responsible for the removal of metabolic waste products from the body. In 2004, there were just under 40,000 incidents of renal cancer and 22,000 deaths across the EU.
Immunotherapy is the treatment to stimulate or restore the ability of the immune (defense) system to fight infection and disease.
1 McDermott DF, Regan MM, Clark JI, et al. Randomized Phase III trial of high-dose interleukin-2 versus subcutaneous interleukin-2 and interferon in patients with metastatic renal cell carcinoma. J Clin Oncol 2005;23(1):133-41
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