Publication

The role of B cell-mediated T cell costimulation in the efficacy of the T cell retargeting bispecific antibody BIS20x3

Stel, AJ., Kroesen, BJ., Jacobs, S., Groen, H., de Leij, LFMH., Kluin-Nelemans, HC. & Withoff, S., 15-Nov-2004, In : Journal of Immunology. 173, 10, p. 6009-6016 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

In this study, we investigated the role of the naturally occurring B cell-mediated T cell costimulation in the antitumor efficacy of the bispecific Ab BIS20x3. BIS20x3 has a dual specificity for both CD20 and CD3 and has previously been shown to effectively direct the lytic potential of cytolytic T cells toward malignant, CD20(+) B cells. BIS20x3 instigated T cell-B cell interaction caused a dose-dependent activation of T cells that was 30 times stronger when compared with T cell activation induced by monovalent anti-CD3 Abs. The activation of T cells by BIS20x3 and B cells appeared functional and resulted in the rapid induction of high lytic potential in freshly isolated peripheral T cells. BIS20x3-mediated T cell-B cell interaction resulted in a significant upregulation of ICAM-1 on B cells and the activation of T cells was found to be dependent on the interaction of ICAM-1 with LFA-1 and trans-activation by the NF-kappaB pathway. Also, the lytic potential of freshly isolated T cells activated via BIS20x3 appeared to be dependent on NF-kappaB signaling in the target B cells. Interestingly, the costimulatory signaling effects described in this study appeared specifically related to the targeting against CD20 because targeting against CD19, by a CD3xCD19-directed bispecific Ab, was significantly less effective in inducing T cell activation and T cell-mediated B cell lysis. Together these results demonstrate that the malignant B cells actively contribute to their own demise upon CD20-directed bispecific Ab-mediated T cell targeting.

Original languageEnglish
Pages (from-to)6009-6016
Number of pages8
JournalJournal of Immunology
Volume173
Issue number10
Publication statusPublished - 15-Nov-2004

    Keywords

  • ANTI-CD20 MONOCLONAL-ANTIBODY, NF-KAPPA-B, MHC CLASS-II, FOLLICULAR LYMPHOMA, OVARIAN-CARCINOMA, INDOLENT LYMPHOMA, PHASE-II, IN-VITRO, RITUXIMAB, EXPRESSION

ID: 4276673