cancer-research

Noe C, McDermott E (2015) Featured Article: SP-SAP human clinical trial for cancer pain – an anesthesiologist’s point of view. Targeting Trends 16(3)

Related Products: SP-SAP (Cat. #IT-07)

Read the featured article in Targeting Trends.

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

Higgins S, Fillmore H, Ashkan K, Butt A, Pilkington G (2015) Dual targeting NG2 and GD3A using Mab-Zap immunotoxin results in reduced glioma cell viability in vitro. Anticancer Res 35:77-84.

Summary: Human glioma-derived cell lines were sequentially incubated with anti-NG2 and anti-GD3A coupled to Mab-ZAP (Cat. #IT-04) at 1 μg/ml and 5 μg/ml for 72 hours each. The combination therapy was significantly more effective than single therapy in eliminating the glioma cells.

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

Ehrlich D, Wang B, Lu W, Dowling P, Yuan R (2014) Intratumoral anti-HuD immunotoxin therapy for small cell lung cancer and neuroblastoma. J Hematol Oncol 7:91. doi: 10.1186/s13045-014-0091-3

Summary: HuD protein is a 40-kDa neuronal RNA-binding protein that is expressed in 100% of small cell lung cancer (SCLC) tumor cells. An anti-HuD monoclonal was biotinylated and combined with Streptavidin-ZAP (Cat. #IT-27); this conjugate was tested both in vitro and in vivo. Anti-HuD-SAP eliminated NCI-H69 and Neuro-2a cells at an EC50 of <0.5 μg/ml. 1 mg/kg of the conjugate injected directly into subcutaneous tumors generated in mice resulted in a temporary lack of tumor growth or regression of the tumor. The results demonstrate the potential of HuD as a therapeutic target for SCLC and neuroblastoma.

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

Pergolizzi J, Gharibo C, Ho K (2015) Treatment considerations for cancer pain: A global perspective. Pain Pract 15:778-792. doi: 10.1111/papr.12253

Summary: This review discusses the treatment of cancer pain, addressing various aspects of the overall picture, such as early pain treatment to reduce central sensitization and chronic pain, pain assessment tools, and guidelines for treating specific populations of patients. Some of the current tools for pain management are discussed, including SP-SAP, which is currently in clinical trials as a cancer pain therapeutic.

Related Products: SP-SAP (Cat. #IT-07)

Frankel AE, Nymeyer H, Lappi DA, Higgins D, Ahn C, Noe C (2014) Preliminary results from a phase I study of substance P-saporin in terminal cancer patients with intractable pain. Journal of Clinical Oncology 32:191. doi: 10.1200/jco.2014.32.31_suppl.191

Summary: Existing pain therapies are insufficient to control cancer pain in 10-15% of patients. Substance P (SP) and its receptor, neurokinin-1 (NK-1r) have been determined to play a major role in spinal transmission of chronic pain. Animal studies have demonstrated that disruption of the NK-1r pathway alleviates chronic pain caused by a variety of stimuli. The authors are conducting a Phase I clinical trial in humans (NCT02036281) assessing the ability of SP-SAP (Cat. #IT-07) to treat intractable chronic pain due to cancer. Patients have received intrathecal injections of 1, 2, or 4 µg of SP-SAP with no evidence of toxicity or neurological or cardiac abnormalities. Doses will escalate up to 90 µg.

Related Products: SP-SAP (Cat. #IT-07)

Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Barnholtz-Sloan JS, Villano JL (2014) Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev 23(10):1985-1996. doi: 10.1158/1055-9965.EPI-14-0275 PMID: 25053711

Objective: The authors report on the current epidemiology of glioblastomas (GBM) with data from the Central Brain Tumor Registry of the United Stated (CBTRUS) as well as discuss the trends in incidence and survival. They provide a review on molecular markers in GBM that helped distinguish the similar subtypes of GBM and have prognostic and predictive value.

Summary: GBM is the most common brain and CNS malignancy, accounting for 45.2% of malignant primary brain and CNS tumors, 54% of all gliomas, and 16% of all primary brain and CNS tumors. GBMs comprise of primary and secondary subtypes which evolve through different genetic pathways, affect patients at different ages and have differences in outcomes. While many studies have investigated the basis of incidence differences by gender, age, race, and risk factors for GBM, many of these studies had inconclusive findings. The field has invested significant resources on the characterization for the various subclassifications of GBM and is in position to advance therapies specific to the genetic abnormalities of each. The success of m-TOR pathway inhibition for subependymal giant-cell astrocytomas and the possibility of identifying a subtype of GBM sensitive to up-front treatment with bevacizumab are examples. The complex molecular changes associated with GBM will likely make personalized therapy challenging. Although clinical advances in GBM are rare, the authors look to the new era in cancer biology we are in for meaningful advances.

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)