**7. Dendritic cell therapy**

Vaccination strategies have been developed that involve dendritic cells (DCs), which are antigen-presenting cells for T-cell activation. The DCs are pulsed with tumor lysate to overcome the shortcomings of autologous DCs. These strategies have shown remarkable anti-tumor activity, with low toxicity, in several cancer types. In the area of MPM, 9 patients received three vaccinations of autologous mature DCs loaded with autologous tumor cell lysate [31]. Among these patients, 3 showed a partial response in the first 8 weeks after the DC vaccination. However, two of those three patients had received chemotherapy before the DC vaccination, which might have influenced the anti-tumor effect. In the next step of treatment, they added cyclophosphamide to increase the anti-tumor activity by inhibiting regulatory T cells [32]. Ten patients with MPM received cyclophosphamide and a vaccination of autologous mature DCs loaded with autologous tumor cell lysate. Of those ten patients, seven lived longer than 24 months, and the mean OS was 37 months.

Obtaining autologous tumor cell lysate is time consuming, because patients have to undergo multiple tumor biopsies. In one study, allogeneic tumor lysate obtained from a tumor cell line was applied to autologous DCs [33]. Nine patients with MPM

were treated with DC vaccinations (autologous DCs pulsed with tumor lysate from five mesothelioma cell lines). Of these, two patients experienced a partial response and all nine patients established disease control. The median OS was longer than 22.8 months. Based on those promising results, an ongoing phase II/III study is currently testing DCs loaded with allogeneic tumor cell lysate as a maintenance therapy after chemotherapy (DENIM trial) [34].
