*5.5. Immunological Arming to Improve Antigen Presentation*

To enable successful tumor-directed T-cell immunity, effective presentation of tumor antigen by DCs needs to be restored. The chemokine GM-CSF promotes maturation and activation of antigen presenting DCs from myeloid precursors. oAds armed with GM-CSF have been used to elicit T-cell mediated antitumoral responses [58,102]. CG0070 is a GM-CSF-armed oncolytic Ad5 involved in clinical investigation as described above. Using Ad5-∆24-GMCSF, Cerullo et al. showed tumor-specific immunity in an immunocompetent syngeneic hamster model [102]. In 20 patients with advanced solid tumors, responses could be observed including two complete tumor responses. The administration of Ad5/3-∆24-GMCSF has been investigated in tumor patients showing a clinical benefit according to RECIST criteria in 8/12 radiologically evaluated individuals. The data revealed that oAd treatment affected immune responses specific for the tumor antigen survivin [103]. A correlation of antitumoral and antiviral immune responses has been confirmed by Kanerva et al. [104]. An oAd expressing both GM-CSF and IL-12 has been used to support the administration of a DC vaccine. Tumor infection with Ad-∆B7/IL12/GMCSF promoted migration of DCs to tumor-draining lymph nodes [105]. However, GM-CSF also has protumorigenic and immunosuppressive functions by recruiting myeloid suppressor cells and impairing immune responses [106,107]. In pancreatic cancer, tumor-released GM-CSF supports the development of an immunosuppressive subset of DCs, which promotes metastasis [108]. Alternative options to improve intratumoral antigen presentation by oAds include the co-expression of Fms-like tyrosine kinase-3 ligand (Flt3L) and GM-CSF [109], or a combination of Flt3L with macrophage inflammatory protein 1α (MIP-1α, CCL3) [110].
