Tumor Immunology, Radboud University Nijmegen Medical Centre.
PURPOSE: Anti-cancer dendritic cell (DC) vaccines require the DC to relocate to lymph nodes (LN) to trigger immune responses. However, these migration rates are typically very poor. Improving the targeting of ex vivo generated DC to LN might increase vaccine efficacy and reduce costs. We investigated DC migration in vivo in humans in different conditions. Experimental design: HLA-A*02:01 melanoma patients were vaccinated with mature DC loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (KLH) (NCT00243594). For this study, patients received an additional intradermal (i.d.) vaccination with 111In-labeled mature DC. The injection site was pretreated with nonloaded, activated DC, TNF or Imiquimod; GM-CSF was co-injected or smaller numbers of DC were injected. Migration was measured by scintigraphy and compared to an intra-patient control vaccination. In an ex vivo tissue model, we measured CCL21-directed migration of 19F-labeled DC over a period of up to 12 hours using 19F MRI to supplement our patient data. RESULTS: Pretreatment of the injection site induced local inflammatory reactions but did not improve migration rates. Both in vitro and in vivo, reduction of cell numbers to 5x10^6 or less cells per injection improved migration. Furthermore, scintigraphy is insufficient to study migration of such small numbers of 111In-labeled DC in vivo. CONCLUSION: Reduction of cell density, not pretreatment of the injection site, is crucial for improved migration of DC to LNs in vivo.