cancer-research

Polito L, Djemil A, Bortolotti M (2016) Plant toxin-based immunotoxins for cancer therapy: a short overview. Biomedicines 4(2):12. doi: 10.3390/biomedicines4020012

Related Products: Saporin (Cat. #PR-01)

Dickey D, Thomas G, Dassie J, Giangrande P (2016) Method for confirming cytoplaintratumoral anti-HuD immunotoxinsmic delivery of RNA aptamers. (eds. Shum K, Rossi J). In: SiRNA Delivery Methods. Methods in Molecular Biology. 1364:209-217. Humana Press, New York, NY. doi: 10.1007/978-1-4939-3112-5_17

Objective: To describe a functional assay (RIP assay) to confirm cellular uptake and subsequent cytoplasmic release of an RNA aptamer which binds to a cell surface receptor expressed on prostate cancer cells (PSMA).

Summary: This publication details an in vitro functional assay to confirm that the aptamer retains function following conjugation to saporin and describe a cellular assay to measure aptamer-mediated saporin-induced cytotoxicity.

Usage: The folded biotinylated aptamer was mixed at a 1:4 molar ratio of Streptavidin-ZAP, confirmed by agarose gel, a PSMA enzymatic activity (NAALADase) assay performed. FGF-SAP was used as a control.

Related Products: Streptavidin-ZAP (Cat. #IT-27), FGF-SAP (Cat. #IT-38)

Sedlik C, Heitzmann A, Viel S, Ait Sarkouh R, Batisse C, Schmidt F, De La Rochere P, Amzallag N, Osinaga E, Oppezzo P, Pritsch O, Sastre-Garau X, Hubert P, Amigorena S, Piaggio E (2016) Effective antitumor therapy based on a novel antibody-drug conjugate targeting the Tn carbohydrate antigen. Oncoimmunology 5:e1171434. doi: 10.1080/2162402X.2016.1171434

Summary: Scientists wanted to study the potential of Chi-Tn, a monoclonal antibody against a glycol-peptidic tumor-associated antigen, as an anticancer antibody-drug conjugate. They demonstrated that Chi-Tn specifically targeted tumor cells in vivo, using flow cytometry and deconvolution microscopy to show that Chi-Tn is rapidly internalized. Chi-Tn-SAP (ATS Custom Services) effectively killed Tn-positive cells, but had no effect on Tn-negative cells. Saporin (Cat. #PR-01) was used as control. The cytotoxicity of the Chi-Tn-SAP correlated with the level of tumoral Tn expression.

Related Products: Saporin (Cat. #PR-01), Custom Conjugates

Yuan X, Yang M, Chen X, Zhang X, Sukhadia S, Musolino N, Bao H, Chen T, Xu C, Wang Q, Santoro S, Ricklin D, Hu J, Lin R, Yang W, Li Z, Qin W, Zhao A (2017) Characterization of the first fully macropinocytosing human antibodies human anti-TEM1 scFv in models of solid tumor imaging and immunotoxin-based therapy. Cancer Immunol Immunother 66:367-378.. doi: 10.1007/s00262-016-1937-z

Summary: Tumor endothelial marker 1 (TEM1) has been identified as a novel surface marker upregulated on the blood vessels and stroma in many solid tumors. The authors previous isolated a single-chain variable fragment (scFv) 78 against TEM1 from a yeast display scFv library and evaluated potential applications of scFv78 as a tool for tumor molecular imaging, immunotoxin-based therapy and nanotherapy. MS1 and MS1-hTEM1 cells were treated with site-specifically biotinylated scFv78 conjugated with the Streptavidin-ZAP (Cat. #IT-27) at a molar ratio of 4:1 (scFv78:ZAP) starting from 40 nM serially diluted down to 0.04 nM. The scFv78-saporin immunoconjugate exerted dose-dependent cytotoxicity with high specificity to TEM1-positive cell in vitro. The data indicate that scFv78, the first fully human anti-TEM1 recombinant antibody, recognizes both human and mouse TEM1 and has features advantageous for the development of imaging probes or antibody-toxin conjugates for a large spectrum of human TEM1-positive solid tumors.

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

Pires E, D’Souza R, Needham M, Herr A, Jazaeri A, Li H, Stoler M, Anderson-Knapp K, Thomas T, Mandal A, Gougeon A, Flickinger C, Bruns D, Pollok B, Herr J (2015) Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a candidate immunotherapeutic target for uterine tumors. Oncotarget 6:30194-30211. doi: 10.18632/oncotarget.4734

Summary: Ovastatin is a zinc matrix metallo-proteinase thought to play roles in sperm-egg interaction and the prevention of polyspermy in eutherians. This protein is not found in normal adult tissues, but is expressed by uterine carcinosarcomas. The authors investigated the possibility of targeting ovastatin as a tumor surface neoantigen for therapeutic purposes. SNU539 cells, a uterine malignant mixed Müllerian tumor-derived cell line, were challenged with 1 μM, 0.1 μM, and 0.01 μM rabbit polyclonal anti-ovastatin coupled to 5.42 nM Fab-ZAP rabbit (Cat. #IT-57). Rabbit IgG-SAP (Cat. #IT-35) was used as a control. The results indicate that for this form of uterine cancer, ovastatin is a viable therapeutic target.

Related Products: Fab-ZAP rabbit (Cat. #IT-57), Rabbit IgG-SAP (Cat. #IT-35)

Damelin M, Bankovich A, Park A, Aguilar J, Anderson W, Santaguida M, Aujay M, Fong S, Khandke K, Pulito V, Ernstoff E, Escarpe P, Bernstein J, Pysz M, Zhong W, Upeslacis E, Lucas J, Lucas J, Nichols T, Loving K, Foord O, Hampl J, Stull R, Barletta F, Falahatpisheh H, Sapra P, Gerber H, Dylla S (2015) Anti-EFNA4 calicheamicin conjugates effectively target triple-negative breast and ovarian tumor-initiating cells to result in sustained tumor regressions. Clin Cancer Res 21:4165-4173. doi: 10.1158/1078-0432.CCR-15-0695

Summary: Triple-negative breast cancer (TNBC) is characterized by tumors lacking HER2, estrogen receptor, and progesterone receptor. TNBC has proved to be very difficult to treat, in large part because of the absence of consensus targets on the surface of the tumor cells. In this work the authors empirically established a set of surface markers associated with TNBC tumor initiating cells, as produced by patient-derived xenografts. Ephrin-A4 was selected as a therapeutic target, and a cell line transfected with the ephrin-A4 gene was challenged with two versions of biotinylated anti-ephrin-A4 coupled to Streptavidin-ZAP (Cat. #IT-27). Both the mouse monoclonal and the humanized antibodies reach an EC50 of 10 ng/ml, indicating that ephrin-A4 has promise as a therapeutic target for TNBC.

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

Li J, Pan Y, Zhang B, Chen Q (2015) Macrophages are needed in the progression of tuberculosis into lung cancer. Tumour Biol 36:6063-6066. doi: 10.1007/s13277-015-3283-8

Summary: Approximately 30% of lung carcinomas also have tuberculosis lesions. The authors investigated the potential link between inflammatory processes and cancer in the lung. Mice with established tuberculosis infections received weekly 20 μg tail vein injections of Mac-1-SAP (Cat. #IT-06) in order to eliminate macrophages. Six months later the mice receiving Mac-1-SAP had a significantly lower incidence of lung carcinoma than control animals.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

Garcia-Castillo M, Tran T, Bobard A, Renard H, Rathjen S, Dransart E, Stechmann B, Lamaze C, Lord M, Cintrat J, Enninga J, Tartour E, Johannes L (2015) Retrograde transport is not required for cytosolic translocation of the B-subunit of Shiga toxin. J Cell Sci 128:2373-2387. doi: 10.1242/jcs.169383

Summary: Bacterial and plant toxins rely on various trafficking pathways to reach intracellular targets. Shiga and Shiga-like toxins have been found to be moved via vesicular transport through several subcellular structures on the way to the cytosol. Shiga toxin (STx) is the cause of hemolytic uremic syndrome, for which there is no effective treatment. In order to better understand the mechanisms of STx membrane translocation the authors used a custom conjugate of the receptor-binding B-subunit of STx (STxB) and saporin (Custom conjugation provided by Advanced Targeting Systems). In vitro assays demonstrated that STxB-SAP did not use retrograde transport to the Golgi complex in order to reach the cytosol. This information has relevance to antigen cross-presentation of antigen-presenting cells.

Related Products: Custom Conjugates

Chua J, Vankemmelbeke M, McIntosh R, Clarke P, Moss R, Parsons T, Spendlove I, Zaitoun A, Madhusudan S, Durrant L (2015) Monoclonal antibodies targeting LecLex-related glycans with potent antitumor activity. Clin Cancer Res 21:2963-2974. doi: 10.1158/1078-0432.CCR-14-3030

Summary: In this work the authors characterized two monoclonal antibodies that target glycans containing Lewis carbohydrate antigens. One of the methods used was to combine varying concentrations of the antibodies with 50 ng mouse Fab-ZAP (Cat. #IT-48) and apply the conjugates to cells for 72 hours. The antibodies were demonstrated to have efficient internalization, supported by potent in vivo anti-tumor activity.

Related Products: Fab-ZAP mouse (Cat. #IT-48)

Bostad M, Olsen C, Peng Q, Berg K, Høgset A, Selbo P (2015) Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization – A minimally invasive cancer stem cell-targeting strategy. J Control Release 206:37-48. doi: 10.1016/j.jconrel.2015.03.008

Summary: Previously the authors demonstrated the use of photochemical internalization of a custom conjugate consisting of a CD133 antibody coupled to saporin (ATS Custom conjugation). Several cancer cell lines were plated, and incubated in the presence of a photosensitizer with either CD133-SAP at 8.6 pM or Saporin (Cat. #PR-01) at 24 pM. The different concentrations equalized the number of saporin molecules in each sample. A light source was used to initiate the internalization of the molecules. The results indicate that this is a viable strategy for the targeted treatment of cancer stem cells.

Related Products: Anti-CD133-SAP (Cat. #IT-82), Saporin (Cat. #PR-01), Custom Conjugates