cancer-research

Berstad MB, Weyergang A, Berg K (2012) Photochemical internalization (PCI) of HER2-targeted toxins: Synergy is dependent on the treatment sequence. Biochim Biophys Acta 1820(12):1849-1858. doi: 10.1016/j.bbagen.2012.08.027

Summary: A majority of patients develop acquired resistance to trastuzumab, the monoclonal antibody recognizing HER2, coupled to a toxin as a breast cancer therapeutic. One of the modes of resistance is that the therapeutic molecule is trapped inside an endocytic vesicle. PCI is a technique that facilitates cytosolic release of molecules in vesicles. The authors investigated the potency of biotinylated trastuzumab combined with streptavidin-ZAP (Cat. #IT-27) on several cell lines.

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

Ye Y, Dang D, Viet CT, Dolan JC, Schmidt BL (2012) Analgesia targeting IB4-positive neurons in cancer-induced mechanical hypersensitivity. J Pain 13(6):524-531. doi: 10.1016/j.jpain.2012.01.006

Summary: DOR (δ opioid receptor) agonists produce minimal side effects and do not lead to tolerance, making them potential alternatives to the widely used μ opioid receptor agonists. Utilizing the fact that DOR’s are expressed by IB4-positive neurons, the authors injected the subarachnoid space between the L4 and L5 vertebrae of rats with 2.4 μg of IB4-SAP (Cat. #IT-10). 3 μg of saporin (Cat. #PR-01) was used as a control. The results indicate that pharmacological agents targeting IB4-positive neurons may have use in cancer pain treatment.

Related Products: IB4-SAP (Cat. #IT-10), Saporin (Cat. #PR-01)

Selbo PK, Weyergang A, Eng MS, Bostad M, Maelandsmo GM, Hogset A, Berg K (2012) Strongly amphiphilic photosensitizers are not substrates of the cancer stem cell marker ABCG2 and provides specific and efficient light-triggered drug delivery of an EGFR-targeted cytotoxic drug. J Control Release 159(2):197-203. doi: 10.1016/j.jconrel.2012.02.003

Summary: Many anti-cancer drugs are substrates of the ATP-binding cassette transporter ABCG2. Unfortunately ABCG2 is also thought to play an important role in multi-drug resistance and the protection of cancer stem cells against chemotherapeutics and photodynamic therapy. This paper examined whether photosensitizers used in photochemical internalization (PCI) are substrates for ABCG2. Streptavidin-ZAP (Cat. #IT-27) was combined with biotinylated EGF and applied to cells in culture; saporin (Cat. #PR-01) was used as a control. The data show that PCI with the EGF-saporin toxin did not utilize ABCG2 to enter cells.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Saporin (Cat. #PR-01)

Mitra N, Banda K, Altheide TK, Schaffer L, Johnson-Pais TL, Beuten J, Leach RJ, Angata T, Varki N, Varki A (2011) SIGLEC12, a human-specific segregating (pseudo)gene, encodes a signaling molecule expressed in prostate carcinomas. J Biol Chem 286(26):23003-23011. doi: 10.1074/jbc.M111.244152

Summary: Siglec 12 (sialic acid-binding immunoglobulin-like lectin 12) is a sugar molecule that has mutated in humans to be inactive, but is active in other primates. The human version is found on some macrophages, various epithelial cell surfaces, and some human carcinoma cell lines. Using Mab-ZAP (Cat. #IT-04) and monoclonal antibodies against Siglec 12, the researchers demonstrated binding and internalization in a prostate cancer cell line, indicating that Siglec 12 may be a target for some cancer therapies.

Related Products: Mab-ZAP (Cat. #IT-04)

Polito L, Bortolotti M, Pedrazzi M, Bolognesi A (2011) Immunotoxins and other conjugates containing saporin-s6 for cancer therapy. Toxins (Basel) 3(6):697-720. doi: 10.3390/toxins3060697 PMID: 22069735

Ancheta LR, Lappi DA (2011) Basigin-2 (EMMPRIN), a prognostic marker, is a dynamic portal of entry into cancer cells. Cancer Res 71(8):5218. Proceedings of the American Association for Cancer Research Annual Meeting, Orlando, FL. doi: 10.1158/1538-7445.AM2011-5218

Related Products: Anti-Basigin2-SAP (Cat. #IT-54)

Read the featured article in Targeting Trends.

Sawada R, Sun SM, Wu X, Hong F, Ragupathi G, Livingston PO, Scholz WW (2011) Human monoclonal antibodies to Sialyl-Lewisa (CA19.9) with potent CDC, ADCC, and antitumor activity. Clin Cancer Res 17(5):1024-1032. doi: 10.1158/1078-0432.CCR-10-2640

Summary: In this work the authors investigated the use of a carbohydrate antigen, sialyl-Lewisa (CA19.9), as a target for cancer therapeutics. Human monoclonal antibodies were generated against CA19.9 and characterized using ELISA and flow cytometry. To assess internalization one antibody, 5B1, was combined with Hum-ZAP (Cat. #IT-22) and applied to CA19.9-expressing BxPC3 cells. The cytotoxicity of the 5B1-Hum- ZAP complex indicates that CA19.9 may be a target for cancer therapy.

Related Products: Hum-ZAP (Cat. #IT-22)

Quadros EV, Nakayama Y, Sequeira JM (2010) Targeted delivery of saporin toxin by monoclonal antibody to the transcobalamin receptor, TCblR/CD320. Mol Cancer Ther 9(11):3033-3040. doi: 10.1158/1535-7163.MCT-10-0513

Summary: Vitamin B12 is necessary for cell proliferation. Cancer cells display an increased expression of TCb1R, the receptor that facilitates the intake of B12. In order to evaluate the potential of using immunotoxins to eliminate cancer cells expressing TCb1R the authors performed a series of in vitro experiments using their monoclonal antibodies plus Mab-ZAP (Cat. #IT-04). The results indicate that this is a viable therapeutic model that causes minimal peripheral damage.

Related Products: Mab-ZAP (Cat. #IT-04)

Wang Y, Mu X, Liu Y, Zhang X, Wu A, Yue Y (2011) NK-1-receptor-mediated lesion of spinal post-synaptic dorsal column neurons might improve intractable visceral pain of cancer origin. Med Hypotheses 76(1):102-104. doi: 10.1016/j.mehy.2010.08.042

Summary: There is evidence that spinal post-synaptic dorsal column neurons begin to express neurokinin-1 receptors after visceral stimulation. The authors discuss using this expression profile to target SSP-SAP (Cat. #IT-11) to these neurons and eliminate them. This use of ‘molecular neurosurgery’ may be a replacement for traditional neurosurgery for the treatment of cancer-related visceral pain.

Related Products: SSP-SAP (Cat. #IT-11)

Kuroda K, Liu H, Kim S, Guo M, Navarro V, Bander NH (2010) Saporin toxin-conjugated monoclonal antibody targeting prostate-specific membrane antigen has potent anticancer activity. Prostate 70(12):1286-1294. doi: 10.1002/pros.21164

Summary: Current treatments for prostate cancer are only moderately effective. In this work the authors examined the cytotoxic efficacy of an anti-prostate-specific membrane antigen (PMSA) antibody conjugated to saporin on PMSA-positive cell lines. hJ591, a humanized anti-PMSA antibody, was biotinylated and combined with streptavidin-ZAP (Cat. #IT-27). The hJ591-streptavidin-ZAP complex was specifically cytotoxic to PMSA-positive cell lines, and had anti-cancer activity in a xenograft model. This work demonstrates the anti-cancer potential of targeting PMSA.

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