This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart 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 Renard, I. Articles by Jacobs, N. Search for Related Content PubMed PubMed Citation Articles by Renard, I. Articles by Jacobs, N.

(American Journal of Pathology. 2002;160:113-122.)
© 2002 American Society for Investigative Pathology

Regular Articles

Anti-CD3/Anti-Epidermal Growth Factor Receptor-Bispecific Antibody Retargeting of Lymphocytes against Human Neoplastic Keratinocytes in an Autologous Organotypic Culture Model

Isabelle Renard^*, Delia Mezzanzanica, Silvana Canevari, Silvano Ferrini, Jacques Boniver^*, Philippe Delvenne^* and Nathalie Jacobs^*

From the Department of Pathology,^*
University of Liège, Liège, Belgium; the Department of Experimental Oncology,
Istituto Nazionale Tumori, Milan, Italy; and the Laboratory of Pharmacology,
Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy

Local cellular immune defects have been described in several tumors including human papillomavirus (HPV)-associated cervical cancer. This observation suggests the potential therapeutic benefit of immune manipulations that restore cellular immunity. Here, we evaluated the ability of bispecific monoclonal antibodies (bimAbs) to redirect T cells against keratinocytes transformed in vitro by HPV in an autologous three-dimensional culture model (organotypic cultures). The epidermal growth factor receptor (EGFR) was chosen as target for an anti-CD3/anti-EGFR bimAb because it is overexpressed in many malignant epithelial lesions and only weakly expressed in the basal layers of normal squamous epithelium. Interestingly, in organotypic cultures, the pattern of expression of EGFR was similar to that observed in vivo. The ability of T cells retargeted by CD3/EGFR bimAb to lyse HPV-transformed cell lines was confirmed in monolayer cultures. In autologous organotypic cultures, an increase in apoptotic HPV⁺ keratinocytes and a significant decrease in the thickness of HPV⁺ organotypic cultures were observed when activated lymphocytes and bimAbs were added to the cultures, whereas organotypic cultures of normal keratinocytes were not significantly affected. These data were similar to those obtained in the allogeneic model. These results suggest the potential usefulness of CD3-EGFR bimAb-retargeted lymphocytes in immunotherapeutic protocols for malignant epithelial lesions.

This article has been cited by other articles:

				P. Hubert, L. Herman, C. Maillard, J.-H. Caberg, A. Nikkels, G. Pierard, J.-M. Foidart, A. Noel, J. Boniver, and P. Delvenne Defensins induce the recruitment of dendritic cells in cervical human papillomavirus-associated (pre)neoplastic lesions formed in vitro and transplanted in vivo FASEB J, September 1, 2007; 21(11): 2765 - 2775. [Abstract] [Full Text] [PDF]

				T. Piazza, E. Cha, I. Bongarzone, S. Canevari, A. Bolognesi, L. Polito, A. Bargellesi, F. Sassi, S. Ferrini, and M. Fabbi Internalization and recycling of ALCAM/CD166 detected by a fully human single-chain recombinant antibody J. Cell Sci., April 1, 2005; 118(7): 1515 - 1525. [Abstract] [Full Text] [PDF]

				P. Hubert, B. Evrard, C. Maillard, E. Franzen-Detrooz, L. Delattre, J.-M. Foidart, A. Noel, J. Boniver, and P. Delvenne Delivery of Granulocyte-Macrophage Colony-Stimulating Factor in Bioadhesive Hydrogel Stimulates Migration of Dendritic Cells in Models of Human Papillomavirus-Associated (Pre)Neoplastic Epithelial Lesions Antimicrob. Agents Chemother., November 1, 2004; 48(11): 4342 - 4348. [Abstract] [Full Text] [PDF]