| |
|
|
|
|
|
|
|||
|
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.
TRANSPLANTATION Vaccination regimens incorporating CpG-containing oligodeoxynucleotides and IL-2 generate antigen-specific antitumor immunity from T-cell populations undergoing homeostatic peripheral expansion after BMT1 Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 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.
This article has been cited by other articles:
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Copyright © 2007 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||