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Increasing inflationary T-cell responses following transient depletion of MCMV-specific memory T cells.
Sims S, Bolinger B, Klenerman P (2015) Increasing inflationary T-cell responses following transient depletion of MCMV-specific memory T cells. Eur J Immunol 45:113-118. doi: 10.1002/eji.201445016
Summary: The standard CD8+ T-cell response to infection is a rapid proliferation followed by a reduction in number after the infection is cleared. Murine cytomegalovirus is an exception in that an infection generates a life-long latency with low-level sporadic replication. Immunodominant cells accumulate over time and stabilize at a high frequency. The authors examined a paradoxical boost following depletion of these cells with an M38 antibody attached to Streptavidin-ZAP (Cat. #IT-27). Mice were treated with 44 pM intraperitoneal injections. M38 is an epitope present on the effector CD8+ T cells. Following a significant depletion of cells, the population rebounded and reached a higher percentage of total CD8+ T-cells than before the depletion.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies.
Ha K, Bidlingmaier S, Zhang Y, Su Y, Liu B (2014) High-content analysis of antibody phage-display library selection outputs identifies tumor selective macropinocytosis-dependent rapidly internalizing antibodies. Mol Cell Proteomics 13:3320-3331. doi: 10.1074/mcp.M114.039768
Summary: Macropinocytosis, the internalization of large endocytic vesicles called macropinosomes, is upregulated in Ras-transformed cancers. To date, large-scale antibody generation strategies have not incorporated a selection method for antibodies. In this work the authors demonstrate screening and validation of the antibodies that utilize the macropinosome pathway. One method used was to biotinylate the antibodies and combine them with Streptavidin-ZAP (Cat. #IT-27) at a 1:1 ratio. The conjugate was applied to cells in a concentration curve starting at 200 nM in order to demonstrate internalization and cell killing.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization.
Bostad M, Kausberg M, Weyergang A, Olsen C, Berg K, Høgset A, Selbo P (2014) Light-triggered, efficient cytosolic release of IM7-saporin targeting the putative cancer stem cell marker CD44 by photochemical internalization. Mol Pharm 11:2764-2776. doi: 10.1021/mp500129t
Summary: CD44 is known as a common cancer stem cell (CSC) marker. Given that CSC’s seem to have the ability to resist many therapeutic agents, the authors investigated the use of photochemical internalization (PCI) while targeting CD44-expressing CSC’s. An immunotoxin was constructed by biotinylating a pan CD44 antibody and combining it with Streptavidin-ZAP (Cat. #IT-27) at a 4:1 biotinylated antibody to Streptavidin-ZAP molar ratio. Various cancer cell lines were incubated with the toxin at a concentration of 0.825 nM. The toxin showed specific cytotoxicity to CD44-expressing cell lines, demonstrating the efficacy of PCI in conjunction with targeted toxins to treat some cancers
Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD44-SAP (Cat. #IT-72)
Depletion of inflammatory dendritic cells with anti-CD209 conjugated to saporin toxin.
Alonso M, Gregorio J, Davidson M, Gonzalez J, Engleman E (2014) Depletion of inflammatory dendritic cells with anti-CD209 conjugated to saporin toxin. Immunol Res 58:374-377. doi: 10.1007/s12026-014-8511-6
Objective: To investigate a strategy that avoids monocyte intermediates to deplete inflammatory dendritic cells (DCs). Mice with an abundance of inflammatory DCs as a consequence of lipopolysaccharide exposure were treated with anti-CD209 antibody conjugated to saporin.
Summary: The results demonstrate depletion of CD209+ DCs. This strategy could prove useful for the targeted reduction of inflammatory DCs in disease.
Usage: Streptavidin-ZAP mixed with biotinylated Anti-CD209 was delivered i.v. to mice. Inflammatory DCs were markedly depleted.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
The novel EpCAM-targeting monoclonal antibody 3-17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines.
Lund K, Bostad M, Skarpen E, Braunagel M, Krauss S, Duncan A, Hogset A, Selbo P (2014) The novel EpCAM-targeting monoclonal antibody 3-17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines. MAbs 6(4):1038-1050. doi: 10.4161/mabs.28207
Summary: The epithelial cell adhesion molecule (EpCAM) is an attractive diagnostic and therapeutic target for a wide range of human carcinomas. It has also been found on cancer stem cells, increasing the interest in targeting and eliminating cells that express it. The authors have created a monoclonal antibody that binds EpCAM, and use several assays to demonstrate the antibody’s potential as an oncology tool. In one series of assays the biotinylated antibody was combined with streptavidin-ZAP (Cat. #IT-27), and in conjunction with photochemical internalization was shown to have specific cytotoxicity on several different cancer cell lines over a range of concentrations.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Deletion of naive T cells recognizing the minor histocompatibility antigen HY with toxin-coupled peptide-MHC class I tetramers inhibits cognate CTL responses and alters immunodominance.
Hess SM, Young EF, Miller KR, Vincent BG, Buntzman AS, Collins EJ, Frelinger JA, Hess PR (2013) Deletion of naive T cells recognizing the minor histocompatibility antigen HY with toxin-coupled peptide-MHC class I tetramers inhibits cognate CTL responses and alters immunodominance. Transpl Immunol 29(1-4):138-145. doi: 10.1016/j.trim.2013.10.005
Summary: The authors utilized biotinylated peptide-MHC class I tetramers with Streptavidin-ZAP (Cat. #IT-27) to selectively delete a specific population of alloreactive T cells in mice. Animals received iv 33-pmol injections of the toxic tetramer, and the data indicate that these toxic tetramers can prevent the induction of donor-specific responses that result in organ rejection.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties.
Bostad M, Berg K, Hogset A, Skarpen E, Stenmark H, Selbo PK (2013) Photochemical internalization (PCI) of immunotoxins targeting CD133 is specific and highly potent at femtomolar levels in cells with cancer stem cell properties. J Control Release 168(3):317-326. doi: 10.1016/j.jconrel.2013.03.023
Summary: Targeted therapies for cancer can be trapped in the lysosome and compartmentalized away from the target. Photochemical internalization is a method to increase the efficacy of these compounds by releasing the therapeutic portion of the molecule from the endocytic vesicles to the cytosol by the use of light. The authors demonstrate this method on cells expressing the cancer stem cell marker CD133. Biotinylated antibodies against CD133 were combined with Streptavidin-ZAP (Cat. #IT-27) and applied to cell lines.
Related Products: Streptavidin-ZAP (Cat. #IT-27)
A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells.
Burgos-Ojeda D, McLean K, Bai S, Pulaski H, Gong Y, Silva I, Skorecki K, Tzukerman M, Buckanovich RJ (2013) A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells. Cancer Res 73(12):3555-3565. doi: 10.1158/0008-5472.CAN-12-2845
Objective: To evaluate tumor vascular markers (TVM) expression in a human embryonic stem cell–derived teratoma (hESCT) tumor model previously shown to have human vessels.
Summary: The model tested represents a useful tool to test anti-human TVM therapy and evaluate in vivo human CSC tumor biology.
Usage: In vitro – Anti-THY1-SAP (biotinylated Anti-THY1 mixed equimolar with Streptavidin-ZAP) was incubated with mesenchymal stem cells (MSC); resulting in statistically significant MSC death. In vivo – Anti-THY1-SAP or control (Rat IgG-SAP) was administered intravenously. Treated ovarian tumors showed delayed growth and significant reduction in central tumor viability.
Related Products: Streptavidin-ZAP (Cat. #IT-27), Rat IgG-SAP (Cat. #IT-17)
Collagen-like cell-penetrating peptides
Yamazaki CM, Nakase I, Endo H, Kishimoto S, Mashiyama Y, Masuda R, Futaki S, Koide T (2013) Collagen-like cell-penetrating peptides. Angew Chem Int Ed Engl 52(21):5497-5500. doi: 10.1002/anie.201301266
Objective: To overcome drawbacks of cell-penetrating peptide (CPP)-conjugated forms, namely instability against attack by proteases, and binding to serum proteins that lowers the availability of the CPP to target cells.
Summary: Complexes were prepared by combining biotinylated CPPs with Streptavidin-ZAP to evaluate the impact of utilizing a rigid collagen-like triple-helical scaffold to improve CPP performance. There was low adsorption onto serum proteins and triple-helical CPPs are extremely stable in animal serum. Such unique properties are expected to be advantageous to long-term applications in cell culture systems and to in vivo drug delivery.
Usage: Biotinylated CPPs were interacted with Streptavidin-ZAP (SA-ZAP); IT-27: Streptavidin-ZAP
Related Products: Streptavidin-ZAP (Cat. #IT-27)
Photochemical internalization of CD133-targeting immunotoxins efficiently depletes sarcoma cells with stem-like properties and reduces tumorigenicity.
Stratford EW, Bostad M, Castro R, Skarpen E, Berg K, Hogset A, Myklebost O, Selbo PK (2013) Photochemical internalization of CD133-targeting immunotoxins efficiently depletes sarcoma cells with stem-like properties and reduces tumorigenicity. Biochim Biophys Acta 1830(8):4235-4243. doi: 10.1016/j.bbagen.2013.04.033
Summary: In this work the authors used photochemical internalization (PCI) to facilitate local cytosolic toxin release from various biotinylated-anti-CD133 antibodies coupled with Streptavidin-ZAP (Cat. #IT-27) in SW872 cells. This technique demonstrates potential for non-invasive sarcoma therapy.
Related Products: Streptavidin-ZAP (Cat. #IT-27)