2015 Targeting Trends Review

Devesa I, Ferrándiz-Huertas C, Mathivanan S, Wolf C, Luján R, Changeux J, Ferrer-Montiel A (2014) αCGRP is essential for algesic exocytotic mobilization of TRPV1 channels in peptidergic nociceptors. Proc Natl Acad Sci U S A 111:18345-18350. doi: 10.1073/pnas.1420252111

Summary: The sensitization of transient receptor potential vanilloid 1 (TRPV1) can lead to the development and maintenance of chronic pathological pain conditions. In this work the authors determined that TRPV1 receptors use membrane insertion mechanisms in order to potentiate neuronal excitability. In order to specifically link this activity to peptidergic neurons the authors treated rat primary dorsal root ganglion cultures with 10 mM rIB4-SAP (Cat. #IT-10) to deplete the non-peptidergic neurons.

Related Products: IB4-SAP (Cat. #IT-10)

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)

Sato M, Inada E, Saitoh I, Matsumoto Y, Ohtsuka M, Miura H, Nakamura S, Sakurai T, Watanabe S (2015) A combination of targeted toxin technology and the piggyBac-mediated gene transfer system enables efficient isolation of stable transfectants in nonhuman mammalian cells. Biotechnol J 10:143-153. doi: 10.1002/biot.201400283

Summary: In this work the authors developed a new transfection strategy that takes advantage of the fact that many cell lines endogenously express α-1,3-galactosyltransferase (α-Gal), the target of rIB4-SAP (Cat. #IT-10). After transfection low expressing or non-transfected cells are killed by an application of rIB4-SAP at 80 μg/ml for 2 hours. The surviving cells eventually express α-Gal again, and require no selective agent to maintain expression of the gene of interest. These transfected cells can be transfected again using the same method.

Related Products: IB4-SAP (Cat. #IT-10)

Read the featured article in Targeting Trends.

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)

Feetham C, Barrett-Jolley R (2014) NK1-receptor-expressing paraventricular nucleus neurones modulate daily variation in heart rate and stress-induced changes in heart rate variability. Physiol Rep 2:e12207. doi: 10.14814/phy2.12207

Summary: Neurons in the paraventricular nucleus (PVN) project to the medulla and spinal cord, regulating heart rate and blood pressure. Although the activity of these neurons becomes elevated during heart failure, their role in overall cardiovascular control is unclear. The authors lesioned the PVN of rats with 2 ng injections of SSP-SAP (Cat. #IT-11). Heart rate variability during the experiment was measured using a high/low frequency ratio in response to psychological stress. The variability response of lesioned rats was lower than that of controls, and a shift in daily heart rate variation was seen as well. The authors conclude that neurokinin-1 expressing neurons in the PVN couple the cardiovascular system to the daily heart rate as well as the sympathetic response to psychological stress.

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

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)

Mang Y, Zhao Z, Zeng Z, Wu X, Li Z, Zhang L (2015) Efficient elimination of CD103-expressing cells by anti-CD103 antibody drug conjugates in immunocompetent mice. Int Immunopharmacol 24:119-127. doi: 10.1016/j.intimp.2014.11.004

Summary: Previous work has demonstrated that an M290-SAP custom conjugate promoted the long-term survival of pancreatic islet allografts by reducing the number of CD103+ cells. M290 is an antibody that targets CD103. Systemic use of the saporin conjugate can result in toxicity and bystander effects to the animal. In this work the authors used M290 conjugated to three different cytotoxic agents in order to avoid these bystander effects. The various reagents were compared in several assays, including internalization studies, flow cytometry, and cytotoxicity studies. The results indicate that the alternative cytotoxic drugs can be used systemically with M290 to eliminate CD103+ cells.

Related Products: Custom Conjugates

Speer C, Sun C, Liets L, Stafford B, Chapman B, Cheng H (2014) Eye-specific retinogeniculate segregation proceeds normally following disruption of patterned spontaneous retinal activity. Neural Dev 9:25. doi: 10.1186/1749-8104-9-25

Summary: The authors administered 0.88-1.66 μg of an Anti-VaChT-SAP custom conjugate to ferrets with an intraocular injection. Although the lesioned animals demonstrated normal eye-specific retinogeniculate development, there were significant abnormalities in spontaneous retinal activity. These differences in activity manifested themselves as eye-specific segregation defects.

Related Products: Custom Conjugates

Kalinchuk A, Porkka-Heiskanen T, McCarley R, Basheer R (2015) Cholinergic neurons of the basal forebrain mediate biochemical and electrophysiological mechanisms underlying sleep homeostasis. Eur J Neurosci 41:182-195. doi: 10.1111/ejn.12766

Summary: Previous work has indicated that non-rapid eye movement during recovery sleep after sleep deprivation requires cholinergic neurons in the BF. The authors examined how BF cholinergic neurons affect the levels of HSP markers during sleep deprivation. Rats received 230-ng injections of 192-IgG-SAP (Cat. #IT-01) into the horizontal limb of the diagonal band/substantia innominata/ magnocellular preoptic area. The results indicate that cholinergic neurons in the BF are important for regulating the biochemical and EEG mechanisms that contribute to HSP.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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)