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This Article Full Text (PDF) All Versions of this Article: jimmunol.0900159v1 183/11/7196    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Filatenkov, A. Articles by Strober, S. PubMed PubMed Citation Articles by Filatenkov, A. Articles by Strober, S.

Ineffective Vaccination against Solid Tumors Can Be Enhanced by Hematopoietic Cell Transplantation¹

Alexander Filatenkov,^2* Antonia M.S. Müller, William Wei-Lin Tseng, Sussan Dejbakhsh-Jones,^* Daniel Winer, Richard Luong, Judith A. Shizuru, Edgar G. Engleman, and Samuel Strober^2*

*Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305; Division of Blood and Bone Marrow Transplantation, Department of Medicine, Stanford University, School of Medicine, Stanford, CA 94305; Department of Pathology, Stanford University School of Medicine, Palo Alto, CA 94304; and Department of Comparative Medicine, Stanford University School of Medicine, Stanford, CA 94305

Vaccination with tumor Ags has not been an effective treatment for solid tumors. The goal of the current study was to determine whether a combination of vaccination and hematopoietic cell transplantation (HCT) can effectively treat primary, disseminated, or metastatic CT26 and MC38 murine colon tumors. Vaccination of tumor-bearing mice with irradiated tumor cells and CpG adjuvant failed to alter progressive tumor growth. However, mice bearing primary, disseminated lung, or metastatic liver tumors were uniformly cured after administration of total body irradiation, followed by the transplantation of hematopoietic progenitor cells and T cells from syngeneic, but not allogeneic vaccinated donors. Requirements for effective treatment of tumors included irradiation of hosts, vaccination of donors with both tumor cells and CpG, transfer of both CD4⁺ and CD8⁺ T cells along with progenitor cells, and ability of donor cells to produce IFN-. Irradiation markedly increased the infiltration of donor T cells into the tumors, and the combined irradiation and HCT altered the balance of tumor-infiltrating cells to favor CD8⁺ effector memory T cells as compared with CD4⁺CD25⁺FoxP3⁺ T regulatory cells. The combination of vaccination and autologous hematopoietic cell transplantation was also effective in treating tumors. In conclusion, these findings show that otherwise ineffective vaccination to solid nonhematologic tumors can be dramatically enhanced by HCT.

² Address correspondence and reprint requests to Dr. Samuel Strober and Dr. Alexander Filatenkov, Stanford University, Division of Immunology and Rheumatology, 269 Campus Drive, Stanford, CA 94305-5166. E-mail addresses: sstrober{at}stanford.edu and afilaten{at}stanford.edu

¹ This work was supported by a grant from the National Cancer Institute (P01 CA-49605) and the Nishimura Fund for Cancer Research.