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*
Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94304; and
Millennium Pharmaceuticals, Cambridge, MA 02139
Dendritic cells (DC) represent potent APCs that are capable
of generating tumor-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 PBMC. DC were cocultured ex vivo with
recombinant mouse prostatic acid phosphatase as the target neoantigen.
Following enrichment, DC developed an activated phenotype with
up-regulation of CD80, CD86, and CD83 expression. During culture, the
DC maintained their levels of various adhesion molecules, including
CD44, LFA-1, cutaneous lymphocyte-associated Ag, and CD49d,
up-regulated CCR7, but lost CD62 ligand and CCR5. In the absence of
CD62 ligand, such cells would not be expected to prime T cells
efficiently if administered i.v. due to their inability to access
lymphoid tissue via high endothelial venules. To assess this
possibility, three patient cohorts were immunized with Ag-pulsed DC by
i.v., intradermal (i.d.), or intralymphatic (i.l.) injection. All
patients developed Ag-specific T cell immune responses following
immunization, regardless of route. Induction of IFN-
production,
however, 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 of Th1-type immunity. Five of nine patients who were
immunized by the i.v. route 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 prime T cell immunity regardless of route,
the quality of this response and induction of Ag-specific Abs may be
affected by the route of administration.
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