HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Challita-Eid, P. M. Articles by Rosenblatt, J. D. Search for Related Content PubMed PubMed Citation Articles by Challita-Eid, P. M. Articles by Rosenblatt, J. D.

A RANTES-Antibody Fusion Protein Retains Antigen Specificity and Chemokine Function¹

Pia M. Challita-Eid^*, Camille N. Abboud^*,, Sherie L. Morrison, Manuel L. Penichet, Karen E. Rosell^*, Tina Poles^*, Shannon P. Hilchey^*, Vicente Planelles^* and Joseph D. Rosenblatt^2,*,

^* Hematology-Oncology Unit, University of Rochester Cancer Center, and Department of Microbiology and Immunology, University of Rochester, Rochester, NY 14642; and Department of Microbiology and Molecular Genetics, Molecular Biology Institute, University of California, Los Angeles, CA 90095

The successful eradication of cancer cells in the setting of minimal residual disease may require targeting of metastatic tumor deposits that evade the immune system. We combined the targeting flexibility and specificity of mAbs with the immune effector function of the chemokine RANTES to target established tumor deposits. We describe the construction of an Ab fusion molecule with variable domains directed against the tumor-associated Ag HER2/neu, linked to sequences encoding the chemokine RANTES (RANTES.her2.IgG3). RANTES is a potent chemoattractant of T cells, NK cells, monocytes, and dendritic cells, and expression of RANTES has been shown to enhance immune responses against tumors in murine models. RANTES.her2.IgG3 fusion protein bound specifically to HER2/neu Ag expressed on EL4 cells and on SKBR3 breast cancer cells as assayed by flow cytometry. RANTES.her2.IgG3 could elicit actin polymerization of THP-1 cells and transendothelial migration of primary T lymphocytes. RANTES.her2.IgG3 prebound to SKBR3 cells also facilitated migration of T cells. RANTES.her2.IgG3 bound specifically to the CCR5 chemokine receptor, as demonstrated by flow cytometry, and inhibited HIV-1 infection via the CCR5 coreceptor. RANTES.her2.IgG3, alone or in combination with other chemokine or cytokine fusion Abs, may be a suitable reagent for recruitment and activation of an expanded repertoire of effector cells to tumor deposits.

This article has been cited by other articles:

				A. B. Fredriksen and B. Bogen Chemokine-idiotype fusion DNA vaccines are potentiated by bivalency and xenogeneic sequences Blood, September 15, 2007; 110(6): 1797 - 1805. [Abstract] [Full Text] [PDF]

				J. M. Roda, R. Parihar, C. Magro, G. J. Nuovo, S. Tridandapani, and W. E. Carson III Natural Killer Cells Produce T Cell-Recruiting Chemokines in Response to Antibody-Coated Tumor Cells Cancer Res., January 1, 2006; 66(1): 517 - 526. [Abstract] [Full Text] [PDF]

				J. Li, P. Hu, L. A. Khawli, and A. L. Epstein Complete Regression of Experimental Solid Tumors by Combination LEC/chTNT-3 Immunotherapy and CD25+ T-Cell Depletion Cancer Res., December 1, 2003; 63(23): 8384 - 8392. [Abstract] [Full Text] [PDF]

				D. Messmer, B. Messmer, and N. Chiorazzi The global transcriptional maturation program and stimuli-specific gene expression profiles of human myeloid dendritic cells Int. Immunol., April 1, 2003; 15(4): 491 - 503. [Abstract] [Full Text] [PDF]

				Y. Zhu, H. A. Gelbard, M. Roshal, S. Pursell, B. D. Jamieson, and V. Planelles Comparison of Cell Cycle Arrest, Transactivation, and Apoptosis Induced by the Simian Immunodeficiency Virus SIVagm and Human Immunodeficiency Virus Type 1 vpr Genes J. Virol., April 15, 2001; 75(8): 3791 - 3801. [Abstract] [Full Text]