Tumour-cell based vaccines Although check details immunization using autologous irradiated tumour cells can deliver a range of tumour antigens to the immune system that may not be present in single-target vaccines and is avoiding the challenges involved in ex vivo propagation of tumour or immune cells, the poor expression, processing and presentation of TAA by tumour cell itself leads to ineffective immunization. Seliciclib Consequently, studies have focused on strategies to enhance the potency of cell based vaccines including transduction of tumour cells with MHC or costimulatory molecules, co-administration of adjuvants such as Bacillus Calmette-Guerin,

and engineering tumour cell vaccines to secrete immunostimulatory cytokines. Among the immunostimulatory cytokines that have been employed in transducing tumour cells, the GM-CSF showed the most promising results [for review, [61]]. GM-CSF can be also produced by mixing irradiated tumour cells with controlled GM-CSF releasing microspheres or bystander GM-CSF producing cells. Tumour cells have been also

engineered to express MHC and/or co-stimulatory molecules, such as B7-1 [62, 63] in order to activate immune cells. None of these techniques have been applied so far to HN cancer, nevertheless tumour-cell based vaccines represent an attractive approach which merits further investigation in order to overcome the hurdle represented RG-7388 supplier by the need to obtain tumour tissue from each patient. Adoptive transfer of active T cells

All the above mentioned vaccine preparation can reach a strong CTL stimulation in vaccinated animals or humans. However, even high levels of CTL did not correlate with the presence of active effector cells within the tumours as the tumour escaping mechanisms are actively fighting the CTL induced by the TAA utilised for immunotherapy. The adoptive transfer of active T cells may overcome the immunotolerance obstacle. This technique relies on the ex vivo activation and expansion of tumour-reactive lymphocytes which are then returned to the Immune system host. Poorly immunogenic established tumours have been cured by ACT in murine models [64–66]. Consequently, similar strategies were transferred into the clinical setting but early studies demonstrated only partial success [67–71]. In more recent approaches ACT was utilised together with strategies to deplete the immune system of endogenous T-cell subpopulations like naturally occurring T regulatory cells or to limit the physical space in transferring cells [71, 72]. By these approaches first successful therapy was reported in a single patient with melanoma metastasis [73] and thereafter in 35 patients was demonstrated an objective clinical response in over 50% of them [74, 75].