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Immunotherapy of recurrent B-cell malignancies after allo-SCT with Bi20 (FBTA05), a trifunctional anti-CD3 x anti-CD20 antibody and donor lymphocyte infusion.
Bone Marrow Transplant. 43, 383-397 (2009)
Donor lymphocyte infusions (DLIs) after allo-SCT displayed limited use in CLL and highly malignant non-Hodgkin'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 mu g) 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 mu g. The cytokine pro. le 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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Adoptive immunotherapy; Donor lymphocyte infusion; Allogeneic transplantation; B-cell malignancies; Bispecific antibody; Versus-host-disease; Metastatic breast-cancer; Bispecific antibodies; Phase-i; Rituximab; Transplantation; Chemotherapy; Leukemia; Therapy; Blood
ISSN (print) / ISBN
0268-3369
e-ISSN
1476-5365
Zeitschrift
Bone Marrow Transplantation
Quellenangaben
Band: 43,
Heft: 5,
Seiten: 383-397
Verlag
Nature Publishing Group
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
CCG Hematopoetic Cell Transplants (IMI-KHZ)