Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes

Morecki, Shoshana; Lindhofer, Horst; Yacovlev, Elena; Gelfand, Yael; Slavin, Shimon

doi:10.1182/blood-2005-07-2738

Cited by 27 publications

(19 citation statements)

References 35 publications

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“…24 Although we escalated the doses of donor cells, GVHD was observed neither in the HLA-identical nor in the haploidentical setting. This might go along with recently published data by Morecki et al 25 in which, the presence of target cells, bispecific antibodies divert potentially tissue-damaging alloreactive cells from host tissues, susceptible to GVHD, to tumor cells. Moreover, escalated doses of Bi20 induced increased serum levels of IL-10, a Th1-antagonizing cytokine, which might additionally contribute to the prevention of the development of GVHD.…”

Section: Discussionmentioning

confidence: 81%

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Buhmann

Simões

Stanglmaier³

et al. 2008

Bone Marrow Transplant

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Donor lymphocyte infusions (DLIs) after allo-SCT displayed limited use in CLL and highly malignant nonHodgkin's lymphoma (NHL). Here we studied whether Bi20 (FBTA05), a novel trifunctional bispecific antibody targeting CD20 on lymphoma cells and CD3 on T cells, could induce GVL responses in combination with DLI or mobilized PBSCT after allogeneic transplantation in these diseases. Six patients (three cases with p53-mutated CLL and three with high-grade NHL (HG-NHL)) refractory to standard therapy were treated with escalating doses of Bi20 (range 10-2000 lg) followed by DLI or SCT. Thereby, all CLL patients showed a prompt but transient clinical and hematological response. In one patient with HG-NHL, we observed a halt in progression for almost 4 months. Side effects (fever, chills and bone pain) were tolerable and appeared at antibody dose levels between 40 and 200 lg. The cytokine profile was characterized by transient increases of IL-6, IL-8 and IL-10. Neither human anti-mouse antibodies nor GVHD developed, allowing repeated treatment courses. In summary, the trifunctional antibody Bi20 induced prompt antitumor responses in extensively pretreated, p53-mutated alemtuzumab and rituximab refractory patients indicating its therapeutic potential.

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Section: Discussionmentioning

confidence: 81%

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Buhmann

Simões

Stanglmaier³

et al. 2008

Bone Marrow Transplant

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“…Several EpCAM (CD326)/CD3-bispecific antibodies have been shown in various mouse models to eradicate established tumors, to redirect tumor-resident T cells for lysis of metastatic human ovarian cancer tissue [24,29] and to effectively treat lung metastasis [30][31][32][33]. In a phase I/II study, advanced ovarian cancer patients were treated with the trifunctional bispecific antibody catumaxomab (anti-EpCAM 9 anti-CD3) resulting in a significant reduction of ascites flow rate [34].…”

Section: Introductionmentioning

confidence: 99%

Lysis of cancer cells by autologous T cells in breast cancer pleural effusates treated with anti-EpCAM BiTE antibody MT110

Witthauer

Schlereth

Brischwein

et al. 2008

Breast Cancer Res Treat

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In the present study, the efficacy of a new drug, i.e. the bispecific single-chain antibody MT110 targeting the epithelial antigen EpCAM and the T-cell antigen CD3 was tested ex vivo in malignant pleural effusions (MPEs). EpCAM ? epithelial cells were found in 78% of the MPEs (n = 18). Ex vivo treatment of seven MPEs resulted in a dose-dependent specific lysis of 37 ± 27% (±SD) EpCAM ? cells with 10 ng/ml (P = 0.03) and 57 ± 29.5% EpCAM ? cells with 1,000 ng/ml MT110 (P = 0.016) after 72 h. As a prerequisite for redirected lysis, stimulation of he autologous CD4 ? and CD8 ? cells in MPE by 1,000 ng/ml MT110 resulted in 21 ± 17% CD4 ? /CD25 ? and 29.4 ± 22% CD8 ? /CD25 ? cells (P = 0.016, respectively) after 72 h. This was confirmed by a 22-fold release of TNF-a and 230-fold release of IFN-c (1,000 ng/ml, 48 h, P = 0.03, respectively). Thus, relapsed breast cancer patients resistant to standard treatment might benefit from targeted therapy using MT110.Keywords Malignant pleural effusion Á Breast cancer Á Bispecific antibody Á EpCAM Á CD3 Á MT110 Á Ex vivo therapy

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“…Preliminary experience with these antibodies is promising and it seems that they might overcome tumor resistance at least in some cases. We consider that the use of bispecific antibodies would be proved more effective in the setting of allogeneic transplantation [30]. Preincubation of donor T-cells with a bispecific antibody with anti-CD3 specificity results in binding of the antibody to effector cells.…”

Section: Bispecific Antibodiesmentioning

confidence: 99%

Monoclonal antibodies in the treatment of lymphoid malignancies

Tsirigotis

Economopoulos

2008

The Journal of Steroid Biochemistry and Molecular Biology

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Use of trifunctional bispecific antibodies to prevent graft versus host disease induced by allogeneic lymphocytes

Cited by 27 publications

References 35 publications

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 × anti-CD20 antibody and donor lymphocyte infusion

Lysis of cancer cells by autologous T cells in breast cancer pleural effusates treated with anti-EpCAM BiTE antibody MT110

Monoclonal antibodies in the treatment of lymphoid malignancies

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