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Role of target antigen in bispecific‐antibody‐mediated killing of human glioblastoma cells: A pre‐clinical study
Author(s) -
Pfosser Achim,
Brandl Martina,
Salih Helmut,
GrosseHovest Ludger,
Jung Gundram
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990209)80:4<612::aid-ijc21>3.0.co;2-k
Subject(s) - antigen , cd28 , cd3 , antibody , cancer research , chondroitin sulfate proteoglycan , biology , t cell , glioma , tumor antigen , microbiology and biotechnology , immunology , immunotherapy , immune system , cd8 , proteoglycan , extracellular matrix
Bispecific antibodies (bsAbs) directed to tumor‐associated antigens and to receptors mediating T‐cell activation, such as the TCR/CD3 complex and the co‐stimulatory CD28 molecule, are capable of activating T cells at the surface of tumor cells, resulting in tumor‐cell killing. Here we report the pre‐clinical characterization of bispecific‐antibody fragments (bsFab 2 ) directed to 2 different glioblastoma‐associated antigens: the EGF receptor (EGFR) and a chondroitin‐sulfate proteoglycan (CSPG). Using cultured glioblastoma cells expressing both target antigens, we found that the ability of anti‐tumor × anti‐CD28 bsFab 2 to mediate “targeted T‐cell co‐stimulation” is superior for constructs targeting the CSPG molecule, correlating with an approximately 6‐fold higher expression level of this antigen on the cell surface. In contrast, bsFab 2 triggering CD3 are more effective if they contain EGFR‐target specificity. This indicates that the activity of anti‐tumor × anti‐CD3 constructs critically depends on properties of the antigen other than its expression level on the cell surface, e.g., its mobility in the membrane. These findings prompted us to use EGFR‐targeting bsFab 2 in an ongoing clinical trial with glioma patients. Int. J. Cancer 80:612–616, 1999. © 1999 Wiley‐Liss, Inc.