Gilabert-Oriol R, Thakur M, Haussmann K, Niesler N, Bhargava C, Görick C, Fuchs H, Weng A (2016) Saponins from Saponaria officinalis L. augment the efficacy of a Rituximab-immunotoxin. Planta Med 82:1525-1531. doi: 10.1055/s-0042-110495

Summary: It is known that triterpenoidal saponins that come from Saponaria officinalis, the plant that saporin comes from, increases the cytotoxicity of saporin by modulating its intracellular trafficking. Investigators wanted to know if this could increase the therapeutic affect of Rituximab-Saporin. In the presence of saponins, Rituximab-Saporin had a 700-fold increase in efficacy. Concentrations of 0.0001-1nM of Anti-CD22-SAP (Cat. #IT-37) and 0.001-10nM of Anti-CD25-SAP (Cat. #IT-24) were also tested in vitro with saponins for comparison. They saw a 170-fold and 25-fold increase in cytotoxicity, respectively. All conjugates were tested on Ramos cells, and differing levels of receptor expression could explain the drastic differences in cytotoxicity enhancement.

Related Products: Anti-CD22-SAP human (Cat. #IT-37), Anti-CD25-SAP human (Cat. #IT-24)

Q: I’m interested in your anti-DBH-saporin toxin for lesioning central catecholaminergic neurons. I see from the product description that the antibody used is a mouse monoclonal – designed to specifically target rat DBH. My interest is to produce targeted lesions in mouse transgenic. Will this product still work specifically? Thanks.

A: Unfortunately, we do not have really good data to support the use of our Anti-DBH-SAP (Cat. #IT-03) in mice. There is significant homology between mouse and rat DBH, however the actual antigen for both the mouse monoclonal we use in the immunotoxin and an alternate unpurified rabbit polyclonal, is native bovine DBH enzyme. For further background information there are two references where our product was used in mice. The references are listed below.

An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+ / CD25+ cells.[1] The sympathetic nervous system can play conflicting roles in collagen-induced arthritis (CIA). CD4+CD25+ T cells can play an immunoregulatory effect in this system depending on the expression of the FoxP3 transcription factor. Mice received 5-µg intraperitoneal injections of anti-DBH-SAP to induce an early sympathectomy. The results indicate that the sympathetic nervous system increases disease severity in CIA by stimulating some of the proinflammatory aspects of CD4+CD25+ T cells.

An opposing time-dependent immune-modulating effect of the sympathetic nervous system conferred by altering the cytokine profile in the local lymph nodes and spleen of mice with type II collagen-induced arthritis.[2] In this work the authors examined the role of the sympathetic nervous system (SNS) in late stages of chronic arthritis. 5 µg intraperitoneal injections of anti-DBH-SAP in mice were used to confirm that previous 6-OHDA injections caused a sympathectomy. The results demonstrate that the SNS supports inflammation during the asymptomatic phase of arthritis, but inhibits inflammation during the chronic symptomatic phase.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

References

1. Harle P et al. An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+ cells. Arthritis Rheum 58:2347-2355, 2008.
2. Harle P et al. An opposing time-dependent immune-modulating effect of the sympathetic nervous system conferred by altering the cytokine profile in the local lymph nodes and spleen of mice with type II collagen-induced arthritis. Arthritis Rheum 52:1305-1313, 2005.

Facciabene A, Peng X, Hagemann IS, Balint K, Barchetti A, Wang L-P, Gimotty PA, Gilks CB, Lal P, Zhang L, Coukos G (2011) Tumour hypoxia promotes tolerance and angiogenesis via CCL28 and Treg cells. Nature 475:226-230. doi: 10.1038/nature10169 PMID: 21753853

Objective: To investigate whether a direct link between tumor hypoxia and tolerance occurs through the recruitment of regulatory cells.

Summary: Tumor hypoxia promotes the recruitment of regulatory T (Treg) cells through induction of expression of the chemokine CC-chemokine ligand 28 (CCL28), which, in turn, promotes tumor tolerance and angiogenesis.

Usage: In vivo depletion of CD4+ CD25+ cells was achieved by intraperitoneal administration of anti-CD25 or an immunotoxin consisting of anti-mouse CCR10 or anti-mouse CCR3 antibody conjugated at an equimolar ratio to Streptavidin–ZAP. Anti-CCR10–SAP depleted 90% of CCR101 or CCR31 cells. Anti-CCR10–SAP suppressed tumour growth and abrogated the effects of CCL28 overexpression, whereas anti-CCR3–SAP had no effect on tumor growth.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

Zikri NN, Schumer E, Wang JJ, Gaughan A, Hadley GA, Moffatt-Bruce SD (2010) Induction of CD4(+)CD25(+) T regulatory cells with CD103 depletion. J Surg Res 163(1):162-168. doi: 10.1016/j.jss.2010.04.021

Summary: CD8+ T cells expressing CD103 have been shown to play a key role in the rejection of renal allografts. Use of M290-SAP (a custom saporin conjugation) allows allograft tolerance even in a completely mismatched islet cell transplant model. Use of 1 mg M290-SAP/kg body weight in mice allowed the authors to characterize the kinetics of M290-SAP and its induction of CD4 CD25 regulatory T cells.

Related Products: Custom Conjugates

Harle P, Pongratz G, Albrecht J, Tarner IH, Straub RH (2008) An early sympathetic nervous system influence exacerbates collagen-induced arthritis via CD4+CD25+ cells. Arthritis Rheum 58:2347-2355. doi: 10.1002/art.23628

Summary: The sympathetic nervous system can play conflicting roles in collagen-induced arthritis (CIA). CD4+CD25+ T cells can play an immunoregulatory effect in this system depending on the expression of the FoxP3 transcription factor. Mice received 5 µg intraperitoneal injections of anti-DBH-SAP (Cat. #IT-03) to induce an early sympathectomy. The results indicate that the sympathetic nervous system increases disease severity in CIA by stimulating some of the proinflammatory aspects of CD4+CD25+ T cells.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Rusterholz C, Henrioud PC, Nabholz M (1999) Interleukin-2 (IL-2) regulates the accessibility of the IL-2-responsive enhancer in the IL-2 receptor alpha gene to transcription factors. Mol Cell Biol 19(4):2681-2689. doi: 10.1128/mcb.19.4.2681 PMID: 10082534

Related Products: CD25 Rat Monoclonal (Cat. #AB-19)

Schnell R, Vitetta E, Schindler J, Barth S, Winkler U, Borchmann P, Hansmann ML, Diehl V, Ghetie V, Engert A (1988) Clinical trials with an anti-CD25 ricin A-chain experimental and immunotoxin (RFT5-SMPT-dgA) in Hodgkin’s lymphoma. Leuk Lymphoma 30:525-537. doi: 10.3109/10428199809057565 PMID: 9711915

Related Products: CD25 Mouse Monoclonal (Cat. #AB-18), Anti-CD25-SAP human (Cat. #IT-24)

Mavroudis DA, Jiang YZ, Hensel N, Lewalle P, Couriel D, Kreitman RJ, Pastan I, Barrett AJ (1996) Specific depletion of alloreactivity against haplotype mismatched related individuals by a recombinant immunotoxin: a new approach to graft-versus-host disease prophylaxis in haploidentical bone marrow transplantation. Bone Marrow Transplant 17:793-799. PMID: 8733700

Related Products: CD25 Mouse Monoclonal (Cat. #AB-18), Anti-CD25-SAP human (Cat. #IT-24)

Lowenthal JW, Corthesy P, Tougne C, Lees R, MacDonald HR, Nabholz M (1985) High and low affinity IL 2 receptors: analysis by IL 2 dissociation rate and reactivity with monoclonal anti-receptor antibody PC61. J Immunol 135(6):3988-3994. PMID: 3934270

Related Products: CD25 Rat Monoclonal (Cat. #AB-19)

Lowenthal JW, Zubler RH, Nabholz M, MacDonald HR (1985) Similarities between interleukin-2 receptor number and affinity on activated B and T lymphocytes. Nature 315(6021):669-672. doi: 10.1038/315669a0 PMID: 3925347

Related Products: CD25 Rat Monoclonal (Cat. #AB-19)