B7-1 (CD80) as target for immunotoxin therapy for Hodgkin's disease

Abstract

Summary In this preclinical study, the potential applicability of an anti-B7-1 immunotoxin (IT) line Raji (IC50 10-11 M), R-S cell lines HDLM2, KM/H2 and L428 and also against a B7-1 -transfected epithelial cell line, A431, whose parental line lacks expression of B7-1. In clonogenic assays with Raji cells or KM/H2 cells, a 3-or 4-log kill, respectively, was observed. No cytotoxicity was found against the B7-1-epithelial and endothelial cell lines or against haematopoietic progenitor cells. In conclusion, an anti-B7-1 immunotoxin was developed that had good cytotoxicity against R-S cell lines and that may be used in the elimination of R-S cells in vivo. A concomitant elimination of activated antigen-presenting cells may avoid development of antitoxin and anti-mouse Ig responses and allow repeated administration.

Immunologic pathomechanism of Hodgkin's lymphoma

“…Inhibitors of the JAK/STAT pathway have been investigated mostly in vitrodspecifically, AZD1480 [97] and lestaurtinib [98]. Targeted therapy against surface receptors of the HRS cells includes anti-RANK ligand antibody and anti-CD80 antibody (galiximab) [99]. Noncellular targets of the microenvironment include extra domain B of fibronectin (ED-B-FN), because it is expressed stronger on newly formed vessels in lymphoma-involved lymph nodes (I 131 -ED-B-FN) [100].…”

Karyotypic dissection of Hodgkin's disease cell lines reveals ectopic subtelomeres and ribosomal DNA at sites of multiple jumping translocations and genomic amplification

“…[16][17][18][19][20][21][22][23][24] Cell culture conditions and the provenance, references, cellular origin and characterization of the remaining cell lines used in this study are given in Ref. 25.…”

Evolving Therapies in Relapsed and Refractory Hodgkin Lymphoma

“…Preclinical data demonstrated that an anti-B7-1 immunotoxin had significant anti-tumor activity in HL-cell lines and minimal toxicity to CD34+ hematopoietic stem cell. 14,15 Galiximab is a primatized IgG1 monoclonal antibody, which binds to CD80 with high affinity and induces cell death via antibody-dependent cell-mediated cytotoxicity (ADCC). Smith et al studied the clinical activity of single agent Galiximab in patients with rel/ref HL not eligible for or had failed HDC-ASCT/AlloSCT.…”