Dendritic cells injected via different routes induce immunity in cancer patients

Dendritic cells (DC) represent potent APCs that are capable of generating t umor-specific immunity. We performed a pilot clinical trial using Ag-pulsed DC as a tumor vaccine, Twenty-one patients with metastatic prostate cancer received two monthly injections of DC enriched and activated from their PB MC. DC were cocultured ex vivo with recombinant mouse prostatic acid phosph atase as the target neoantigen, Following enrichment, DC developed an activ ated phenotype with up-regulation of CD80, CD86, and CD83 expression. Durin g culture, the DC maintained their levels of various adhesion molecules, in cluding CD44, LFA-1, cutaneous lymphocyte-associated Ag, and CD49d, up-regu lated CCR7, but lost CD62 ligand and CCR5, In the absence of CD62 ligand, s uch cells would not be expected to prime T cells efficiently if administere d i.v. due to their inability to access lymphoid tissue via high endothelia l venules, To assess this possibility, three patient cohorts were immunized with Ag-pulsed DC by i.v., intradermal (i.d.), or intralymphatic (i.l.) in jection, All patients developed Ag-specific T cell immune responses followi ng immunization, regardless of route. Induction of IFN-gamma production, ho wever, was seen only with i.d. and i.l. routes of administration, and no IL -4 responses were seen regardless of route, consistent with the induction o f Th1-type immunity. Five of nine patients who were immunized by the i.v. r oute developed Ag-specific Abs compared with one of six for i.d. and two of six for i.l. routes, These results suggest that while activated DC can pri me T cell immunity regardless of route, the quality of this response and in duction of Ag-specific Abs may be affected by the route of administration.