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Blood, 1 July 2007, Vol. 110, No. 1, pp. 450-460.
Prepublished online as a Blood First Edition Paper on March 19, 2007; DOI 10.1182/blood-2006-11-057935.
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Submitted November 28, 2006
Accepted March 16, 2007
Vaccination regimens incorporating CpG-containing oligodeoxynucleotides and IL-2 generate antigen-specific anti-tumor immunity from T cell populations undergoing homeostatic peripheral expansion after BMT
James N. Kochenderfer*, Jessica L. Simpson, Christopher D. Chien, and Ronald E. Gress
Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
* Corresponding author; email: kochendj{at}mail.nih.gov.
Development of CD8+ T cell responses targeting tumor-associated antigens after autologous stem cell transplants (ASCT) 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 transplants (BMT) on thymectomized mice then vaccinated the mice with peptides plus CpG-containing oligodeoxynucleotides (CpG) in incomplete Freund's 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 anti-tumor immunity. This is the first report to demonstrate that CD8+ T cell responses capable of executing anti-tumor immunity can be elicited by CpG-containing vaccines during HPE.

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