Drug-free macromolecular therapeutics induce apoptosis in cells isolated from patients with B cell malignancies with enhanced apoptosis induction by pretreatment with gemcitabine

Abstract

Informed consent. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.

Advanced nanomedicines for the treatment of inflammatory diseases

“…To overcome resistance or production of antibodies which may occur after treatment with Rituximab (anti-CD20), another interesting approach was developed by Kopeček et al who developed polymer prodrugs to target B cells. This approach, initially tested for B-cell malignancy treatment [137][138][139][140], was recently evaluated in a pre-clinical model of inflammatory rheumatoid arthritis (RA) [141]. The treatment, tested in a collagen-induced rheumatoid arthritis in mice, was composed of two conjugates: (i) a bispecific engager, Fab′-MORF1 (obtained by linking Fab′ fragment of CD20 mAb to the 3′ end of a morpholino oligonucleotide (MORF1) via a thioether bond) and (ii) a receptor crosslinking mediated by HPMA-based P-(MORF2).…”

Neurosurgery at the crossroads of immunology and nanotechnology. New reality in the COVID-19 pandemic

“…One design was a composition of multiple anti-CD20 antibody Fab’ fragments attached to N -(2-hydroxypropyl)methacrylamide (HPMA) copolymer [288] , [289] . In another design, receptor crosslinking was mediated by the biorecognition of binding motifs (coiled-coil peptides, or complementary oligonucleotides) at the cell surface [290] , [291] , [292] , [293] , [294] , [295] , [296] , [297] , [298] , [299] , [300] , [301] , [302] , [303] , [304] , [305] , [306] . Crosslinking of CD20 initiates apoptosis by calcium influx and mitochondrial signaling pathway without the involvement of toxins or cytotoxic drugs [304] , [306] .…”

“…In another design, receptor crosslinking was mediated by the biorecognition of binding motifs (coiled-coil peptides, or complementary oligonucleotides) at the cell surface [290] , [291] , [292] , [293] , [294] , [295] , [296] , [297] , [298] , [299] , [300] , [301] , [302] , [303] , [304] , [305] , [306] . Crosslinking of CD20 initiates apoptosis by calcium influx and mitochondrial signaling pathway without the involvement of toxins or cytotoxic drugs [304] , [306] . The DFMT was effective in vitro [290] , [291] , [292] , [294] , [295] , [296] , [297] , [298] , [299] , [300] , [301] , [302] , [304] , [306] , in vivo [293] , [295] , [300] , and on cells isolated from patients diagnosed with various subtypes of B cell malignancies [299] , [300] , [303] .…”

“…Crosslinking of CD20 initiates apoptosis by calcium influx and mitochondrial signaling pathway without the involvement of toxins or cytotoxic drugs [304] , [306] . The DFMT was effective in vitro [290] , [291] , [292] , [294] , [295] , [296] , [297] , [298] , [299] , [300] , [301] , [302] , [304] , [306] , in vivo [293] , [295] , [300] , and on cells isolated from patients diagnosed with various subtypes of B cell malignancies [299] , [300] , [303] . DFMT induced apoptosis in 65.9% cells from patients irrespective of genomic aberrations (13q14; 17p13; and 11q22 deletions) [303] .…”

Crosslinking of CD38 Receptors Triggers Apoptosis of Malignant B Cells

“…Hybridization of MORF1/MORF2-mediated receptor crosslinking initiates apoptosis (Scheme 1). We have demonstrated the efficacy of DMFT on CD20 positive (CD20+) Raji B cells in vitro [14,15], in vivo on a disseminated non-Hodgkin lymphoma (NHL) model in SCID mice [16,17], and on patient cells diagnosed with various blood borne malignancies [18]. Apoptosis induction by DMFT is triggered by relocation of crosslinked CD20 complexes to lipid rafts resulting in calcium influx, mitochondrial depolarization, and caspase 3 activation [19].…”