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Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
The MS2 RNA was used as a model by the characterization of the depurination activity of saporin (Barbieri et al. 1994), a ribosome-inactivating protein that appeared as a representative of the multigene family of proteins in various parts of the Saponaria officinalis plant. Interest in the ribosome-inactivating proteins (RIPs), which were produced in fact not only by plants, but also by bacteria and fungi, grew recently in connection with their potent anti-HIV activity (Yadav and Batra 2015).
Marrow Purging And Stem Cell Preparation
Published in Siegfried Matzku, Rolf A. Stahel, Antibodies in Diagnosis and Therapy, 2019
Denis C. Roy, Nadine Beauger, Martin Gyger
In an attempt to facilitate the use of mAbs by rendering them directly cytotoxic, several groups have developed immunoconjugates. Thus, M195, an anti-CD33 mAb, conjugated with iodine 131 was able to target marrow cells and demonstrated significant leukemic cytoreduction after in vivo administration (Schwartz et al., 1993). However, with a range of β-emission of approximately 50 cell diameters, ex vivo purging with such radioactive conjugates would most likely cause irreversible damage to bystander-stem cells, preventing their in vitro use. Immunotoxins (ITs) represent another alternative, and Myers et al. were the first to produce an IT directed against AML cells by conjugating AML-2-23 (anti-CD14) and MCS-2 (anti-CD13) mAbs to the ribosome-inactivating phytotoxin, ricin (Myers et al., 1988). Ricin consists of two subunits, the A and B chains, which are linked by a single disulfide bond as well as noncovalent interactions (Vitetta et al., 1987; Blakey and Thorpe, 1988). The A chain is an enzyme which inactivates the 60S subunit of eukaryotic ribosomes, and the B chain binds to galactose-terminated oligosaccharides that are ubiquitous on eukaryotic cell surfaces. Thus, lactose was added in vitro to block non-specific binding of the whole ricin fraction of the ITs to normal cells (Myers et al., 1988). Both ITs selectively bound to target cells, inhibited protein synthesis, and prevented the clonogenic growth of fresh marrow blasts from AML patients as well as KG-1 (AML) cells. Tecce et al. rather used saporin emitoxin (SAP) conjugates, which demonstrated low cytotoxicity in unconjugated form, and highly specific cytotoxicity and favorable pharmacokinetic properties once conjugated to LAM3 and LAM7 mAbs (Tecce et al., 1991). These ITs yet suffered from a narrow spectrum of activity against monocytes and M5b AML. Nevertheless, the fact that immunotoxins do not necessitate the complicated standardization procedures associated with complement use, nor the sophisticated apparatus required for magnetic purging methods, warrants further developments in this field (Arbour et al., 1996).
Bispecific antibody approach for EGFR-directed blockade of the CD47-SIRPα “don’t eat me” immune checkpoint promotes neutrophil-mediated trogoptosis and enhances antigen cross-presentation
Published in OncoImmunology, 2020
Mark A. J. M. Hendriks, Emily M. Ploeg, Iris Koopmans, Isabel Britsch, Xiurong Ke, Douwe F. Samplonius, Wijnand Helfrich
Treatment of EGFRpos/CD47pos cancer cells with bsAb CD47xEGFR-IgG1 resulted in a prolonged displacement of EGFR and CD47 molecules from the cancer cell surface for 48 h and 24 h, respectively (Figure 2b). After treatment of FaDu cancer cells with CD47xEGFR-IgG1 for 24 h, residual cell surface presence of EGFR and CD47 dropped down to ~50% and ~60%, respectively (Figure 2b–d). Moreover, a potent approximately twofold increase (p < .01) in saporin-mediated apoptotic cell death in NCI-H292 cancer cells was induced by ´piggybacking´ of the Fab-ZAP toxin on internalizing bsAb CD47xEGFR-IgG1 molecules. When using bsAbs MockxEGFR-IgG1 or CD47xMock-IgG1 a lower increase in apoptosis was observed of ~60% (ns) or ~40% (p < .05), respectively (Figure 2e). Additionally, confocal microscopy images of NCI-H292 cells treated with bsAb CD47xEGFR-IgG1 for 24 h, clearly show reduced CD47 and EGFR cell surface presence (Figure 2f). Taken together, these data demonstrated that bsAb CD47xEGFR-IgG1 strongly inhibits cancer cell proliferation and induces prolonged displacement of both EGFR and CD47 from the cancer cell surface.