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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wild, M. K. Articles by Meuer, S. C. Search for Related Content PubMed PubMed Citation Articles by Wild, M. K. Articles by Meuer, S. C.

Tumor Therapy with Bispecific Antibody: The Targeting and Triggering Steps Can Be Separated Employing a CD2-Based Strategy

Martin K. Wild^1,*, Wolfgang Strittmatter^1,, Siegfried Matzku, Burkhart Schraven^* and Stefan C. Meuer^2,*

^* Institute for Immunology, Ruprecht-Karls-Universitaet, Heidelberg, Germany; and E. Merck, Biomed Fo, Darmstadt, Germany

For tumor therapy with unprimed effector cells, we developed a novel combination of a CD2 x tumor Ag bispecific targeting Ab and an anti-CD2 triggering Ab. These Ab constructs were derived from two novel CD2 mAbs, termed M1 and M2 that, together, but not individually activate T cells. Unlike many other CD2 Abs, M1 and M2 do not interfere with TCR/CD3 triggering nor do they inhibit binding of CD2 to its ligand CD58, thus preserving the physiological functions of these important effector cell molecules. M2 was chemically conjugated with an Ab recognizing the epidermal growth factor-receptor (EGF-R). Incubation of unprimed peripheral blood mononuclear cells with the bispecific F(ab')₂ construct (M2xEGF-R) in the presence of trigger Ab M1 led to efficient selective lysis of EGF-R-positive targets by CTL and NK cells. Importantly, the need for trigger Ab M1 for effector cell stimulation allowed to separate targeting from triggering steps in vitro and should thus enable to focus immune responses to sites of target Ag expression in vivo.

This article has been cited by other articles:

				K. Schlienger, C. S. Chu, E. Y. Woo, P. M. Rivers, A. J. Toll, B. Hudson, M. V. Maus, J. L. Riley, Y. Choi, G. Coukos, et al. TRANCE- and CD40 Ligand-matured Dendritic Cells Reveal MHC Class I-restricted T Cells Specific for Autologous Tumor in Late-Stage Ovarian Cancer Patients Clin. Cancer Res., April 1, 2003; 9(4): 1517 - 1527. [Abstract] [Full Text] [PDF]