Vaccination Regimens Incorporating CpG-containing Oligodeoxynucleotides and IL-2 Generate Antigen-specific Antitumor Immunity from T-cell Populations Undergoing Homeostatic Peripheral Expansion After BMT

Development of CD8(+) T-cell responses targeting tumor-associated antigens after autologous stem cell transplantations (ASCTs) might eradicate residual tumor cells and decrease relapse rates. Because thymic function dramatically decreases with aging, T-cell reconstitution in the first year after ASCT in middle-aged patients occurs primarily by homeostatic peripheral expansion (HPE) of mature T cells. To study antigen-specific T-cell responses during HPE, we performed syngeneic bone marrow transplantations (BMTs) on thymectomized mice and then vaccinated the mice with peptides plus CpG-containing oligodeoxynucleotides (CpGs) in incomplete Freund adjuvant and treated the mice with systemic interleukin-2 (IL-2). When CD8(+) T-cell responses were measured ex vivo, up to 9.1% of CD8(+) T cells were specific for tumor-associated epitopes. These large T-cell responses were generated by synergism between CpG and IL-2. When we injected mice subcutaneously with tumor cells 14 days after BMT and then treated them with peptide + CpG-containing vaccines plus systemic IL-2, survival was increased and tumor growth was inhibited in an epitope-specific manner. Depletion of CD8(+) T cells eliminated epitope-specific antitumor immunity. This is the first report to demonstrate that CD8(+) T-cell responses capable of executing antitumor immunity can be elicited by CpG-containing vaccines during HPE.