The state of the art: immune-mediated mechanisms of monoclonal antibodies in cancer therapy

A number of antibody products have now become accepted as effective anti-cancer therapies. Despite being mainly designed to act by inhibiting functional tumour antigens, there is increasing evidence that Fc-mediated engagement of the immune system is an important contributor to the efficacy of several of these therapies. The optimisation of this engagement offers the potential not only to augment efficacy against existing targets, but also to exploit non-functional tumour antigens. Antibodies that achieve efficacy wholly or predominantly through Fc-mediated mechanisms, represent rich opportunities for future therapeutics in oncology. This mini review summarises some of the key challenges, which need to be addressed to select the most effective molecules. These include the identification of optimal antibody characteristics and improvement of the drug discovery process, in particular, the relevance and predictive power of existing in vitro and in vivo screening methods. Advances in our understanding of tumour immunobiology and successful application of technologies designed to enhance immune system engagement will further aid this process

Cell-cycle inhibition and apoptosis induced by curcumin and cisplatin or oxaliplatin in human ovarian carcinoma cells.

Alteration of appropriate cell-cycle progression and of closely related apoptotic process is a basic feature of tumour cells, and development of new tumour-targeted agents focus on apoptosis, either during cell-cycle arrest or following premature cell-cycle checkpoint exit. Increasingly, epidemiological and experimental studies suggest that curcumin protects against cancer, not only because of its well-known antioxidant properties, but also because it modulates intracellular signalling, which is related to cell proliferation and apoptosis. Cisplatin and oxaliplatin are first-line drugs in treatment of many types of epithelial cancer and their combination with other cytostatics are under investigation to limit their side effects and resistance to them. OBJECTIVES: The aim of this study was to evaluate effects of a combined treatment using curcumin with cisplatin or with oxaliplatin, in a human ovarian cancer cell line (2008) and in its cisplatin-resistant variant (C13). RESULTS: Curcumin per se caused concentration-dependent (0.1-100 microm) and time-persistent (24-72 h) reduction in cell proliferation, as well as altered cell cycle parameters and induced apoptosis, in both cell lines. When carcinoma cells were simultaneously exposed to curcumin and to cisplatin or oxaliplatin (at concentrations lower than IC(50)) cell viability was reduced more than with single-drug treatment. Moreover, dose and time related effects of curcumin, when combined with platinum drugs, were linked to consistent reduction in cell cycling and increased apoptosis, in comparison with single-drug treatment. These effects were significant both in wild type and in cisplatin-resistant cells, indicating that curcumin was also able to increase sensitivity of resistant ovarian cancer cells to cisplatin. CONCLUSIONS: The data suggests that curcumin is an interesting natural compound capable of limiting cell proliferation and possibly increasing clinical impact of platinum drugs, in ovarian cancer patients