2014 Targeting Trends Review

Alvarez P, Green P, Levine J (2014) Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat. Pain 155:1161-1167. doi: 10.1016/j.pain.2014.03.004

Summary: In order to better understand where monocyte chemoattractant protein 1 (MCP-1) fits in the chronic pain landscape the authors performed a series of experiments using antisense and mismatch oligodeoxynucleotides against the MCP-1 receptor in rats. Some animals also received 3.2 μg intrathecal injections of IB4-SAP (Cat. #IT-10). IB4-SAP treatment removed water avoidance stress-induced muscle hyperalgesia, as well as preventing stress-induced hyperalgesic priming that is a usual response to administration of MCP-1. The data indicate that MCP-1 takes action through its receptors on IB4+ nociceptors.

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

Ogawa S, Nathan FM, Parhar IS (2014) Habenular kisspeptin modulates fear in the zebrafish. Proc Natl Acad Sci U S A 111(10):3841-3846. doi: 10.1073/pnas.1314184111

Summary: The peptide kisspeptin can be found in several areas of the brain, but its role in regions other than the hypothalamus has not been studied. Zebrafish express kiss1 mRNA which is a conserved ortholog of the mammalian KISSI/KissI making zebrafish a viable model for investigating the role of kisspeptin in various brain systems. Animals received 1 μg of the custom conjugate kiss-SAP (see NK3-SAP, Cat. #IT-63) via an intracranial injection. Blank-SAP (Cat. #IT-21) was used as a control. Reducing Kiss1 immunoreactivity in the habenula and the raphe reduced an invoked fear response, indicating a role for kisspeptin in fear inhibition.

Related Products: Blank-SAP (Cat. #IT-21), NKB-SAP (Cat. #IT-63), Custom Conjugates

Lee SC, Seo KW, Kim HJ, Kang SW, Choi HJ, Kim A, Kwon BS, Cho HR, Kwon B (2015) Depletion of alloreactive T cells by anti-CD137-saporin immunotoxin. Cell Transplant 24:1167-1181. doi: 10.3727/096368914X679327

Summary: The ability to selectively remove T cells that mediate graft-versus-host disease (GVHD) would prevent graft rejection as well as preserve the T cells that mediate graft-versus-leukemia (GVL) effect – especially in cases of hematopoietic stem cell transplantation. In this work the authors used a custom conjugate of anti-mouse CD137 and saporin to eliminate alloreactive T cells during a T cell donor transfer in mice. Rat IgG-SAP (Cat. #IT-17) was used as a control. Transfer of T cells after the immunotoxin treatment did not cause GVHD, but the GVL effect was left intact, indicating the potential of selective T cell depletion for transplantation.

Related Products: Rat IgG-SAP (Cat. #IT-17)

Sato M, Miyoshi K, Nagao Y, Nishi Y, Ohtsuka M, Nakamura S, Sakurai T, Watanabe S (2014) The combinational use of CRISPR/Cas9-based gene editing and targeted toxin technology enables efficient biallelic knockout of the α-1,3-galactosyltransferase gene in porcine embryonic fibroblasts. Xenotransplantation 21:291-300. doi: 10.1111/xen.12089

Summary: Results indicate that a combination of the CRISPR/Cas9 system and targeted toxin technology using IB4-SAP allows efficient enrichment of genome-edited clones, particularly bi-allelic KO clones.

Usage: Cells were trypsinized 3 days after transfection and approximately 80% were incubated for 30 min at 37°C in a solution (25 mcL) containing 0.5–1.0 mcg IB4-SAP.

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

Lund K, Bostad M, Skarpen E, Braunagel M, Krauss S, Duncan A, Hogset A, Selbo P (2014) The novel EpCAM-targeting monoclonal antibody 3-17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines. MAbs 6(4):1038-1050. doi: 10.4161/mabs.28207

Summary: The epithelial cell adhesion molecule (EpCAM) is an attractive diagnostic and therapeutic target for a wide range of human carcinomas. It has also been found on cancer stem cells, increasing the interest in targeting and eliminating cells that express it. The authors have created a monoclonal antibody that binds EpCAM, and use several assays to demonstrate the antibody’s potential as an oncology tool. In one series of assays the biotinylated antibody was combined with streptavidin-ZAP (Cat. #IT-27), and in conjunction with photochemical internalization was shown to have specific cytotoxicity on several different cancer cell lines over a range of concentrations.

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

Li AJ, Wang Q, Dinh TT, Powers BR, Ritter S (2014) Stimulation of feeding by three different glucose-sensing mechanisms requires hindbrain catecholamine neurons. Am J Physiol Regul Integr Comp Physiol 306(4):R257-R264. doi: 10.1152/ajpregu.00451.2013

Summary: The glucoregulatory system of the brain requires catecholamine neurons in the hindbrain. he sensory mechanisms and connected circuitry controlling the response to glucose deficit are not well understood. In order to investigate different drugs that stimulate food intake but interfere with cellular glucose metabolism and transport the authors administered 82 ng of anti-DBH-SAP (Cat. #IT-03) into the paraventricular nucleus as bilateral injections. Saporin (Cat. #PR-01) was used as a control. Lesioned animals did not increase food intake in response to any of the drugs, indicating that stimulation of food intake is activated through a catecholamine-dependent pathway.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Saporin (Cat. #PR-01)

Ye Y, Bae S, Viet CT, Troob S, Bernabe D, Schmidt BL (2014) IB4(+) and TRPV1(+) sensory neurons mediate pain but not proliferation in a mouse model of squamous cell carcinoma. Behav Brain Funct 10(1):5. doi: 10.1186/1744-9081-10-5

Objective: To evaluate subtypes of sensory neurons involved in cancer pain and proliferation.

Summary: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

Usage: IB4(+) neurons play an important role in cancer-induced mechanical allodynia, while TRPV1 mediates cancer-induced thermal hyperalgesia. Characterization of the sensory fiber subtypes responsible for cancer pain could lead to the development of targeted therapeutics.

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

Ljubojevic V, Luu P, De Rosa E (2014) Cholinergic contributions to supramodal attentional processes in rats. J Neurosci 34(6):2264-2275. doi: 10.1523/JNEUROSCI.1024-13.2014

Summary: Previous work has shown that cholinergic transmission is important for attentional processing of visual stimuli. It is not known whether the role of the cholinergic system is specifically in visual processing, or if it is involved in all types of attentional processing. The authors administrated bilateral 40 ng injections of 192-IgG-SAP (Cat. #IT-01) to the nucleus basalis magnocellularis of rats. Animals had been previously trained on both visual and olfactory 5-choice serial reaction time tasks. Lesioned animals displayed deficits on both the visual and olfactory tasks when the attentional demand of the task was increased. The data suggest a modular cortical network that services both visual and olfactory attentional processes.

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

Suto T, Severino AL, Eisenach JC, Hayashida KI (2014) Gabapentin increases extracellular glutamatergic level in the locus coeruleus via astroglial glutamate transporter-dependent mechanisms. Neuropharmacology 81C:95-100. doi: 10.1016/j.neuropharm.2014.01.040

Summary: Gabapentin is effective in reducing acute and chronic pain, but the mechanisms by which it works are not well understood. The authors assessed extracellular glutamate levels and glutamate interaction with several different cellular membrane proteins. Rats received a 0.25 μg injection of anti-DBH-SAP (Cat. #IT-03) into the locus coeruleus (LC) in order to deplete noradreline levels. Mouse IgG-SAP (Cat. #IT-18) was used as a control. The gabapentin-induced glutamate increase in the LC was not affected by the lesion, supporting data indicating that gabapentin induces glutamate release from astrocytes to stimulate descending inhibition.

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Laursen B, Mork A, Plath N, Kristiansen U, Frank Bastlund J (2014) Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration. Brain Res 1543:253-262. doi: 10.1016/j.brainres.2013.10.055

Summary: The Tg2576 mouse strain provides a limited model for Alzheimer’s disease because they do not display degeneration of cholinergic neurons in the basal forebrain – the other main hallmark of Alzheimer’s disease in humans. Using 0.9 μg icv injections of mu p75-SAP (Cat. #IT-16) the authors evaluated mice that had both Aβ deposition and cholinergic depletion. The data show that these mice display cognitive decline and compromised cholinergic levels, creating a viable model for Alzheimer’s disease.

Related Products: mu p75-SAP (Cat. #IT-16)