This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kudo-Saito, C. Articles by Hodge, J. W. Search for Related Content PubMed PubMed Citation Articles by Kudo-Saito, C. Articles by Hodge, J. W.

The Requirement of Multimodal Therapy (Vaccine, Local Tumor Radiation, and Reduction of Suppressor Cells) to Eliminate Established Tumors

Authors' Affiliation: ¹ Laboratory of Tumor Immunology and Biology, and ² Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Jeffrey Schlom, Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, 10 Center Drive, Room 8B09, Bethesda, MD 20892. Phone: 301-496-4343; Fax: 301-496-2756; E-mail: js141c{at}nih.gov.

Purpose: Numerous immune-based strategies are currently being evaluated for cancer therapy in preclinical models and clinical trials. Whereas many strategies look promising in preclinical models, they are often evaluated before or shortly following tumor implantation. The elimination of well-established tumors often proves elusive. Here we show that a multimodal immune-based therapy can be successfully employed to eliminate established tumors.

Experimental Design: This therapy consists of vaccines directed against a self-tumor-associated antigen, the use of external beam radiation of tumors to up-regulate Fas on tumor cells, and the use of a monoclonal antibody (mAb) to reduce levels of CD4⁺CD25⁺ suppressor cells.

Results: We show here for the first time that (a) antigen-specific immune responses induced by vaccines were optimally augmented when anti-CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb administration in combination with vaccines equally augmented T-cell immune responses specific for a self-antigen as well as those specific for a non–self antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced antigen-specific immune responses, it was not sufficient to eliminate established tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti-CD25 mAb regimen was required for the elimination of established tumors; and (e) T cells from mice receiving the combination therapy showed significantly higher T-cell responses specific not only for the antigen in the vaccine but also for additional tumor-derived antigens (p53 and gp70).

Conclusions: These studies reported here support the rationale for clinical trials employing multimodal immune-based therapies.

Key Words: vaccine • CD25 • suppressor cells • immunotherapy • radiation

This article has been cited by other articles:

				R. J. Lechleider, P. M. Arlen, K.-Y. Tsang, S. M. Steinberg, J. Yokokawa, V. Cereda, K. Camphausen, J. Schlom, W. L. Dahut, and J. L. Gulley Safety and Immunologic Response of a Viral Vaccine to Prostate-Specific Antigen in Combination with Radiation Therapy when Metronomic-Dose Interleukin 2 Is Used as an Adjuvant Clin. Cancer Res., August 15, 2008; 14(16): 5284 - 5291. [Abstract] [Full Text] [PDF]

				R. Bos, S. van Duikeren, T. van Hall, M. M. Lauwen, M. Parrington, N. L. Berinstein, B. McNeil, C. J. M. Melief, J. S. Verbeek, S. H. van der Burg, et al. Characterization of Antigen-Specific Immune Responses Induced by Canarypox Virus Vaccines J. Immunol., November 1, 2007; 179(9): 6115 - 6122. [Abstract] [Full Text] [PDF]

				M. T. Litzinger, R. Fernando, T. J. Curiel, D. W. Grosenbach, J. Schlom, and C. Palena IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity Blood, November 1, 2007; 110(9): 3192 - 3201. [Abstract] [Full Text] [PDF]

				K. G. Elpek, C. Lacelle, N. P. Singh, E. S. Yolcu, and H. Shirwan CD4+CD25+ T Regulatory Cells Dominate Multiple Immune Evasion Mechanisms in Early but Not Late Phases of Tumor Development in a B Cell Lymphoma Model J. Immunol., June 1, 2007; 178(11): 6840 - 6848. [Abstract] [Full Text] [PDF]