TNFα contributes to the antitumor activity of a bispecific, trifunctional antibody

Reinhard Zeidler, Anna Mayer, Olivier Gires, Bärbel Schmitt, Brigitte Mack, Horst Lindhofer, Barbara Wollenberg, Annette Walz*

*Corresponding author for this work
24 Citations (Scopus)

Abstract

Immunological cancer therapies focus on the activation of immune effector cells yielding a specific antitumor activity. Disseminated tumor cells are regarded as the origin of metastases and consequently their elimination is the central objective of adjuvant immune therapies. The use of bispecific antibodies is an approach that is regarded as promising in order to fight those disseminated tumor cells. Unfortunately, the efficiency of these antibodies is limited by the fact that they usually activate a single class of effector cell, thus not yielding optimal immune response. In addition, tumor cells may down-regulate the antibody's target molecule and escape recognition. We have recently described results with an intact bispecific molecule, BiUII, that represents a new class of intact antibodies. These antibodies, termed "triomabr®", provide an excellent antitumor activity in vitro, a fact that most probably is attributable to the simultaneous activation of different classes of immune effector cells. We have now investigated this antitumor activity in more detail and demonstrate here that at least a dual mechanism accounts for triomab-mediated killing of tumor cells: besides direct cell-mediated killing, triomab induces the production of TNFα in PBMCs at concentrations that induce apoptosis in target cells. This bystander effect may be of special interest for the clinical application of triomab in terms of killing of target antigen-negative tumor cells.

Original languageEnglish
JournalAnticancer Research
Volume21
Issue number5
Pages (from-to)3499-3503
Number of pages5
ISSN0250-7005
Publication statusPublished - 2001

Fingerprint

Dive into the research topics of 'TNFα contributes to the antitumor activity of a bispecific, trifunctional antibody'. Together they form a unique fingerprint.

Cite this