Genetically modified tumour vaccines: an obstacle race to break host tolerance to cancer

The development of genetically modified tumour vaccines (GMTV) has been pro mpted by a better understanding of antitumour immune responses and genetic engineering technologies, as well as the identification of numerous tumour antigens (TA) in several malignancies which occasionally induce spontaneous tumour regressions. Cellular vaccines are based on autologous or allogenei c tumour cells genetically engineered to secrete different cytokines, co-st imulatory molecules, or allogeneic ELA molecules in order to provide a stro ng stimulatory signal together with the presented TA. Another promising app roach that is targeted towards breaking immune tolerance to TA, exploits de ndritic cells (DC) loaded or genetically modified with TA (and sometimes cy tokines). Effective nonviral and viral gene delivery systems have been cons tructed including a third generation of adenoviral, lentiviral and hybrid v ectors. Studies in mice demonstrated that therapeutic, curative immune resp onses might be elicited by GMTV. Promising results from animal studies are rarely seen in human trials. Several reasons, such as numerous escape mecha nisms of slowly evolving spontaneous tumours and immune incompetence of adv anced patients, are major concerns. Improved monitoring of immune responses to GMTV is essential to distinguish between responders and non-responders in order to tailor immune therapy strategy to the individual patient.