scholarly journals Cytotoxicity of a cell-reactive immunotoxin containing ricin A chain is potentiated by an anti-immunotoxin containing ricin B chain.

1984 ◽  
Vol 160 (1) ◽  
pp. 341-346 ◽  
Author(s):  
E S Vitetta ◽  
R J Fulton ◽  
J W Uhr
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Ricin A Chain ◽  
Daudi Cell ◽  
A Cell ◽  
A Chain ◽  
Ricin A

In vitro killing of the human Daudi cell line by either univalent [F(ab')] or divalent (IgG) forms of rabbit anti-human Ig (RAHIg) coupled to ricin A chain can be specifically potentiated by a "piggyback" treatment with ricin B chain coupled to goat anti-rabbit Ig (GARIg). When cells are treated with univalent immunotoxin (IT) [F(ab') RAHIg-A] and then cultured, IT can be detected on the cell surface for at least 5 h, since GARIg-B can still enhance killing at this time. These results provide a strategy for in vivo use of A chain- and B chain-containing IT.

Immunotoxins up to the present day

1989 ◽  
Vol 9 (2) ◽  
pp. 139-156 ◽  
Author(s):  
Francis A. Drobniewski
Keyword(s):  
Clinical Studies ◽  
Polyclonal Antibodies ◽  
Cell Binding ◽  
Ricin A Chain ◽  
Future Role ◽  
A Chain ◽  
Ricin A

Immunotoxins consist of monoclonal or polyclonal antibodies conjugated to bacterial or plant toxins. The toxins used are typically of the A-B type in which a toxic A chain is coupled to a B chain responsible for cell binding and facilitation of A chain entry into the cytosol. Two broad strategies have been followed: coupling intact toxins, or A chains alone, to antibodies. This review examines current progress in in vitro and in vivo research, including recent clinical studies, concentrating principally on ricin or ricin A chain conjugates. The future role of conjugates using membrane-acting toxins, immunolysins, is also discussed.

Selective killing of smooth muscle cells in culture by the ricin A-chain conjugated with monoclonal antibodies to a cell surface antigen via a dextran bridge

1985 ◽  
Vol 41 (10) ◽  
pp. 1342-1344 ◽  
Author(s):  
O. Yu. Printseva ◽  
A. I. Faerman ◽  
A. V. Maksimenko ◽  
A. G. Tonevitsky ◽  
O. B. Ilynsky ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Monoclonal Antibodies ◽  
Cell Surface ◽  
Smooth Muscle Cells ◽  
Surface Antigen ◽  
Muscle Cells ◽  
Ricin A Chain ◽  
A Cell ◽  
A Chain ◽  
Ricin A

Cyclosporin A and cyclosporin SDZ PSC 833 enhance anti-CD5 ricin A- chain immunotoxins in human leukemic T cells

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 482-489 ◽  
Author(s):  
JP Jaffrezou ◽  
BI Sikic ◽  
G Laurent
Keyword(s):  
Cyclosporin A ◽  
Small Population ◽  
High Dose ◽  
Ricin A Chain ◽  
Psc 833 ◽  
A Chain ◽  
Ricin A ◽  
Sdz Psc 833

Abstract Recent studies have shown that cyclosporin A (CsA) may affect ricin A- chain immunotoxin (RTA-IT) therapy. In this study, we evaluated the ability of CsA and its nonimmunosuppressive analog, SDZ PSC 833, to enhance anti-CD5 T101 RTA-ITs in vitro. Both 4 mumol/L CsA and 4 mumol/L SDZ PSC 833 significantly and specifically enhanced the cytotoxic activity of T101 RTA-IT on the human lymphoblastic T-cell line, CEM III (101-fold and 105-fold, respectively). Furthermore, these Cs also enhanced the cytotoxicity of the more potent T101 F(ab')2 RTA- IT (ninefold and eightfold, respectively). The effect of human plasma, originating from four patients enrolled in a phase I high-dose CsA regimen, was examined on T101 RTA-IT cytotoxicity on CEM III cells. In each case, with plasma CsA levels between 3,090 and 4,860 ng/mL (2.5 to 4 mumol/L), a significant increase in T101 RTA-IT-mediated cytotoxicity was observed ranging from 31% to 60%. Neither CsA nor SDZ PSC 833 affected the rate of RTA-IT binding, internalization, intracellular trafficking, or degradation. Analysis of internalized T101 RTA-IT molecules showed that these were essentially intact, which suggests that these enhancers may act only on a small population of RTA-ITs that escapes present investigational techniques. In conclusion, because the concentrations used are clinically achievable, Cs appear to be promising agents for in vivo enhancement of RTA-ITs.

scholarly journals Cyclosporin A and cyclosporin SDZ PSC 833 enhance anti-CD5 ricin A- chain immunotoxins in human leukemic T cells

Blood ◽  
1994 ◽  
Vol 83 (2) ◽  
pp. 482-489
Author(s):  
JP Jaffrezou ◽  
BI Sikic ◽  
G Laurent
Keyword(s):  
Cyclosporin A ◽  
Small Population ◽  
High Dose ◽  
Ricin A Chain ◽  
Psc 833 ◽  
A Chain ◽  
Ricin A ◽  
Sdz Psc 833

Recent studies have shown that cyclosporin A (CsA) may affect ricin A- chain immunotoxin (RTA-IT) therapy. In this study, we evaluated the ability of CsA and its nonimmunosuppressive analog, SDZ PSC 833, to enhance anti-CD5 T101 RTA-ITs in vitro. Both 4 mumol/L CsA and 4 mumol/L SDZ PSC 833 significantly and specifically enhanced the cytotoxic activity of T101 RTA-IT on the human lymphoblastic T-cell line, CEM III (101-fold and 105-fold, respectively). Furthermore, these Cs also enhanced the cytotoxicity of the more potent T101 F(ab')2 RTA- IT (ninefold and eightfold, respectively). The effect of human plasma, originating from four patients enrolled in a phase I high-dose CsA regimen, was examined on T101 RTA-IT cytotoxicity on CEM III cells. In each case, with plasma CsA levels between 3,090 and 4,860 ng/mL (2.5 to 4 mumol/L), a significant increase in T101 RTA-IT-mediated cytotoxicity was observed ranging from 31% to 60%. Neither CsA nor SDZ PSC 833 affected the rate of RTA-IT binding, internalization, intracellular trafficking, or degradation. Analysis of internalized T101 RTA-IT molecules showed that these were essentially intact, which suggests that these enhancers may act only on a small population of RTA-ITs that escapes present investigational techniques. In conclusion, because the concentrations used are clinically achievable, Cs appear to be promising agents for in vivo enhancement of RTA-ITs.

Factors Controlling Electropermeabilisation of Cell Membranes

2002 ◽  
Vol 1 (5) ◽  
pp. 319-327 ◽  
Author(s):  
M. P. Rols ◽  
M. Golzio ◽  
B. Gabriel ◽  
J. Teissié
Keyword(s):  
Cell Surface ◽  
Electric Field ◽  
Pulse Duration ◽  
Cell Membranes ◽  
Physical Parameters ◽  
Local Exchange ◽  
Physical Mechanisms ◽  
A Cell

Electric field pulses are a new approach for drug and gene delivery for cancer therapy. They induce a localized structural alteration of cell membranes. The associated physical mechanisms are well explained and can be safely controlled. A position dependent modulation of the membrane potential difference is induced when an electric field is applied to a cell. Electric field pulses with an overcritical intensity evoke a local membrane alteration. A free exchange of hydrophilic low molecular weight molecules takes place across the membrane. A leakage of cytosolic metabolites and a loading of polar drugs into the cytoplasm are obtained. The fraction of the cell surface which is competent for exchange is a function of the field intensity. The level of local exchange is strongly controlled by the pulse duration and the number of successive pulses. The permeabilised state is long lived. Its lifetime is under the control of the cumulated pulse duration. Cell viability can be preserved. Gene transfer is obtained but its mechanism is not a free diffusion. Plasmids are electrophoretically accumulated against the permeabilised cell surface and form aggregates due to the field effect. After the pulses, several steps follow: translocation to the cytoplasm, traffic to the nucleus and expression. Molecular structural and metabolic changes in cells remain mostly poorly understood. Nevertheless, while most studies were established on cells in culture ( in vitro), recent experiments show that similar effects are obtained on tissue ( in vivo). Transfer remains controlled by the physical parameters of the electrical treatment.

Effect of Chemical Deglycosylation on the in vivo Fate of Ricin A-Chain

1986 ◽  
Vol 3 (3) ◽  
pp. 189-196 ◽  
Author(s):  
DAVID C. BLAKEY ◽  
PHILIP E. THORPE
Keyword(s):  
Ricin A Chain ◽  
A Chain ◽  
Chemical Deglycosylation ◽  
Ricin A

scholarly journals The effect of strontium ranelate on titanium particle-induced periprosthetic osteolysis regulated by WNT/β-catenin signaling in vivo and in vitro

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Bolun Wang ◽  
Haohui Guo ◽  
Tianxiang Geng ◽  
Kening Sun ◽  
Liang Zhang ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Aseptic Loosening ◽  
Cell Line ◽  
Conditioned Medium ◽  
Strontium Ranelate ◽  
Cell Model ◽  
Periprosthetic Osteolysis ◽  
A Cell

Abstract Aseptic loosening following periprosthetic osteolysis is the primary complication that limits the lifetime of total joint arthroplasty (TJA). The wear particles trigger a chronic inflammation response in the periprosthetic tissue and turn over the bone balance to bone resorption. The present study aimed to investigate the possible effect and mechanism of strontium ranelate (SR), a clinically safe drug for osteoporosis, on particle-induced periprosthetic osteolysis. Thirty-six female C57BL/6j mice underwent tibial Ti-nail implantation to establish an animal model of aseptic loosening. After 12 weeks, micro-CT results showed that strontium ranelate could inhibit periprosthetic bone resorption. In vitro, Ti particles were used to stimulate RAW264.7 cell line to collect conditioned medium, and co-culture MC3T3-E1 cell line with conditioned medium to establish a cell model of aseptic loosening. The results of alkaline phosphatase (ALP) detection, immunofluorescence, and flow cytometry demonstrated that strontium ranelate could regulate the expression of OPG/RANKL, promote differentiation and mineralization, and inhibit apoptosis in osteoblasts. Moreover, we revealed that SR’s exerted its therapeutic effect by down-regulating sclerostin, thereby activating the Wnt/β-catenin signal pathway. Therefore, this research suggests that strontium ranelate could be a potential drug for the prevention and treatment of particle-induced aseptic loosening post-TJA.

scholarly journals Retinoic acid disrupts the Golgi apparatus and increases the cytosolic routing of specific protein toxins.

1994 ◽  
Vol 125 (4) ◽  
pp. 743-753 ◽  
Author(s):  
Y N Wu ◽  
M Gadina ◽  
J H Tao-Cheng ◽  
R J Youle
Keyword(s):  
Retinoic Acid ◽  
Golgi Apparatus ◽  
Retinoic Acid Receptor ◽  
Receptor Activation ◽  
Marker Enzyme ◽  
Ricin A Chain ◽  
Acid Receptor ◽  
A Chain ◽  
Ricin A

All-trans retinoic acid can specifically increase receptor mediated intoxication of ricin A chain immunotoxins more than 10,000 times, whereas fluid phase endocytosis of ricin A chain alone or ricin A chain immunotoxins was not influenced by retinoic acid. The immunotoxin activation by retinoic acid does not require RNA or protein synthesis and is not a consequence of increased receptor binding of the immunotoxin. Vitamin D3 and thyroid hormone T3, that activate retinoic acid receptor (RAR) cognates, forming heterodimers with retinoid X receptor (RXR), do not affect the potency of immunotoxins. Among other retinoids tested, 13-cis retinoic acid, which binds neither RAR nor RXR, also increases the potency of the ricin A chain immunotoxin. Therefore, retinoic acid receptor activation does not appear to be necessary for immunotoxin activity. Retinoic acid potentiation of immunotoxins is prevented by brefeldin A (BFA) indicating that in the presence of retinoic acid, the immunotoxin is efficiently routed through the Golgi apparatus en route to the cytoplasm. Directly examining cells with a monoclonal antibody (Mab) against mannosidase II, a Golgi apparatus marker enzyme, demonstrates that the Golgi apparatus changes upon treatment with retinoic acid from a perinuclear network to a diffuse aggregate. Within 60 min after removal of retinoic acid the cell reassembles the perinuclear Golgi network indistinguishable with that of normal control cells. C6-NBD-ceramide, a vital stain for the Golgi apparatus, shows that retinoic acid prevents the fluorescent staining of the Golgi apparatus and eliminates fluorescence of C6-NBD-ceramide prestained Golgi apparatus. Electron microscopy of retinoic acid-treated cells demonstrates the specific absence of any normal looking Golgi apparatus and a perinuclear vacuolar structure very similar to that seen in monensin-treated cells. This vacuolization disappears after removal of the retinoic acid and a perinuclear Golgi stacking reappears. These results indicate that retinoic acid alters intracellular routing, probably through the Golgi apparatus, potentiating immunotoxin activity indepedently of new gene expression. Retinoic acid appears to be a new reagent to manipulate the Golgi apparatus and intracellular traffic. As retinoic acid and immunotoxins are both in clinical trials for cancer therapy, their combined activity in vivo would be interesting to examine.

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