cancer-research

Palchaudhuri R, Saez B, Hoggatt J, Schajnovitz A, Sykes D, Tate T, Czechowicz A, Kfoury Y, Ruchika F, Rossi D, Verdine G, Mansour M, Scadden D (2016) Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745. doi: 10.1038/nbt.3584

Summary: To demonstrate correction of a clinically relevant disease, we employed CD45-SAP in a mouse model of sickle cell anemia and demonstrated our method achieved >90% donor cell chimerism, all mice in three groups (18/18), resulting in complete disease correction (red blood cell counts, hemoglobin levels, hematocrit levels and reticulocyte frequencies were returned to normal). If these pre-clinical results can be successfully translated to the clinic, it would greatly reduce conditioning-related toxicities and expand the use of hematopoietic stem cell transplantation.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD45.2-SAP (Cat. #IT-91)

Read the featured article in Targeting Trends.

Palchaudhuri R (2016) Featured Article: Targeted depletion of hematopoietic stem cells promises safer transplantation. Targeting Trends 17(3)

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

Read the featured article in Targeting Trends.

See Also:

• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.
• Skulimowska I et al. The biology of hematopoietic stem cells and its clinical implications. FEBS J 16192, 2021.

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)

Lee SB, Frattini V, Bansal M, Castano AM, Sherman D, Hutchinson K, Bruce JN, Califano A, Liu G, Cardozo T, Iavarone A, Lasorella A (2016) An ID2-dependent mechanism for VHL inactivation in cancer. Nature 529(7585):172-177. doi: 10.1038/nature16475 PMID: 26735018

Usage: Western blot

Related Products: Trans-4-Hydroxy-L-Proline Rabbit Polyclonal, Conjugated (Cat. #AB-T044)

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)