Phase 1 trial of a novel anti-CD20 fusion protein in pretargeted radioimmunotherapy for B-cell non-Hodgkin lymphoma

Abstract

Pretargeted radioimmunotherapy (PRIT) has the potential to increase the dose of radionuclide delivered to tumors while limiting radiation to normal tissues. The purpose of this phase 1 trial is to assess safety of this multistep approach using a novel tetrameric single-chain anti-CD20-streptavidin fusion protein (

Photochemically stimulated drug delivery increases the cytotoxicity and specificity of EGF–saporin

“…However, EGF linked to saporin (1:1) through the streptavdin-biotin bond would form an affinity toxin with a MW of ~100 kDa, more suitable for in vivo use. The biotin-streptavidin bond has been clinically used (Knox et al 2000, Weiden 2002, Forero et al 2004, Gruaz-Guyon et al 2005, however, immunogenicity of streptavdin is a major disadvantage of this conjugation strategy (Meredith & Buchsbaum 2006). As described above, PCI will probably be clinically applied in a limited number of times (1-2), and therefore streptavidin-induced immunogenicity may not be a treatment obstacle.…”

Antibody-targeted radiation cancer therapy

“…However, the greatest caveat remains the immunogenicity of the streptavidin component, which limits repeat therapies. This aspect, in part, might be obviated by application of the mAb fragment-streptavidin fusion protein tetramer; however, use of these engineered proteins remains to be fully evaluated 87 . One variation on pre-targeting has been the application of bispecific mAbs that bind to the cell and to a therapeutic element simultaneously 88 .…”

A Method to Correct for Radioactivity in Large Vessels That Overlap the Spine in Imaging-Based Marrow Dosimetry of Lumbar Vertebrae

“…These patients were selected to span the wide range of blood clearance times observed with various radiopharmaceuticals to assess the impact of radioactivity in blood vessels on image quantification of lumbar vertebral marrow. Although 111 In-B9E9 pretarget (14) and 131 I-HuCC49DCh2 (13) patients had relatively fast blood clearance and were expected to have less background contribution to marrow image quantification, 111 In-ibritumomab tiuxetan (12) and 111 In-CC49 (15) patients had slower blood clearance and were expected to have more background contribution to marrow image quantification. The patient selection criteria included abdominal CT images that covered lumbar vertebrae L2 through L4 for vessel volume measurement, serial blood samples that allowed determination of radioactivity in blood vessels, and a relatively wide range of patient body size.…”

“…The details of the radiopharmaceuticals and their administration have previously been reported (12)(13)(14)(15). These patients were selected to span the wide range of blood clearance times observed with various radiopharmaceuticals to assess the impact of radioactivity in blood vessels on image quantification of lumbar vertebral marrow.…”