References

Hay C, Sult E, Huang Q, Mulgrew K, Fuhrmann S, McGlinchey K, Hammond S, Rothstein R, Rios-Doria J, Poon E, Holoweckyj N, Durham N, Leow C, Diedrich G, Damschroder M, Herbst R, Hollingsworth R, Sachsenmeier K (2016) Targeting CD73 in the tumor microenvironment with MEDI9447. Oncoimmunology 5:e1208875. doi: 10.1080/2162402X.2016.1208875

Summary: MEDI9447 is a human monoclonal antibody that is specific for the ectoenzyme CD73 and currently undergoing Phase I clinical trials. Here the authors show that MEDI9447 is a potent inhibitor of CD73 ectonucleotidase activity, with wide ranging immune regulatory consequences. MEDI9447 results in relief from adenosine monophosphate (AMP)-mediated lymphocyte suppression in vitro and inhibition of mouse syngeneic tumor growth in vivo. In contrast with other cancer immunotherapy agents such as checkpoint inhibitors or T-cell agonists, MEDI9447 drives changes in both myeloid and lymphoid infiltrating leukocyte populations within the tumor microenvironment of mouse models. In vitro experiments validating the internalization of antibodies into cell lines MDA-MB-231 and 4T1 were measured using the Fab-ZAP human antibody internalization kit (Cat. #KIT-51-Z). Combination data showing additive activity between MEDI9447 and anti-PD-1 antibodies using human cells in vitro and mouse tumor models further demonstrate the potential value of relieving adenosine-mediated immunosuppression. Based on these data, a Phase I study to test the safety, tolerability, and clinical activity of MEDI9447 in cancer patients was initiated (NCT02503774).

Related Products: Fab-ZAP human (Cat. #IT-51)

Lim J, Stafford B, Nguyen P, Lien B, Wang C, Zukor K, He Z, Huberman A (2016) Neural activity promotes long-distance, target-specific regeneration of adult retinal axons. Nat Neurosci 19:1073-1084. doi: 10.1038/nn.4340 PMID: 27399843

Summary: Axons in the CNS fail to regenerate after injury. Scientists sought to identify strategies that would allow retinal ganglion cell (RGC) axons to regenerate in the eye-to-brain pathway, and if that was possible, whether the axons could reconnect with their correct targets and restore visual function. It was previously shown that increasing mTOR signaling could trigger RGC axon regeneration. Several conditions were tested, but combining increased mTOR signaling and then exposing mice to high-contrast visual stimulation daily for 3 weeks scientists after optic nerve crush resulted in long distance RGC axon regeneration, re-innervation of the brain and partial recovery of a subset of visual behaviors. A 1:1000 dilution of Anti-Melanopsin (Cat. #AB-N38) was used for the immunohistochemical analysis of retinas, optic nerves and brain tissue.

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Gilabert-Oriol R, Thakur M, Haussmann K, Niesler N, Bhargava C, Görick C, Fuchs H, Weng A (2016) Saponins from Saponaria officinalis L. augment the efficacy of a Rituximab-immunotoxin. Planta Med 82:1525-1531. doi: 10.1055/s-0042-110495

Summary: It is known that triterpenoidal saponins that come from Saponaria officinalis, the plant that saporin comes from, increases the cytotoxicity of saporin by modulating its intracellular trafficking. Investigators wanted to know if this could increase the therapeutic affect of Rituximab-Saporin. In the presence of saponins, Rituximab-Saporin had a 700-fold increase in efficacy. Concentrations of 0.0001-1nM of Anti-CD22-SAP (Cat. #IT-37) and 0.001-10nM of Anti-CD25-SAP (Cat. #IT-24) were also tested in vitro with saponins for comparison. They saw a 170-fold and 25-fold increase in cytotoxicity, respectively. All conjugates were tested on Ramos cells, and differing levels of receptor expression could explain the drastic differences in cytotoxicity enhancement.

Related Products: Anti-CD22-SAP human (Cat. #IT-37), Anti-CD25-SAP human (Cat. #IT-24)

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.

Jiao J, Xiong W, Wang L, Yang J, Qiu P, Hirai H, Shao L, Milewicz D, Chen Y, Yang B (2016) Differentiation defect in neural crest-derived smooth muscle cells in patients with aortopathy associated with bicuspid aortic valves. EBioMedicine 10:282-290. doi: 10.1016/j.ebiom.2016.06.045 PMID: 27394642

Summary: Individuals with bicuspid aortic valves (BAV) are at a higher risk of developing thoracic aortic aneurysms (TAA) than patients with trileaflet aortic valves (TAV). Aneurysms associated with BAV most commonly involve the ascending aorta. Smooth muscle cells (SMCs) in the ascending and descending aorta arise from neural crest (NC) and paraxial mesoderm (PM), respectively. Scientists hypothesized defective differentiation of the neural crest stem cells (NCSCs)-derived SMCs but not paraxial mesoderm cells (PMCs)- derived SMCs contributes to the aortopathy associated with BAV. Induced pluripotent stem cells (iPSCs) from BAV/TAA patients were differentiated into NCSC-derived SMCs and showed decreased expression of a marker of SMC differentiation (MYH11) and impaired contraction. The scientists demonstrated that decreased differentiation and contraction of patient’s NCSC-derived SMCs may contribute to the aortopathy associated with BAV.

Usage: Anti-NGFr (ME20.4, p75, Cat. #AB-N07) was used for the immunofluorescence staining and flow cytometry of NCSCs.

Related Products: NGFr (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07)

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.

Go J, Kim JE, Kwak MH, Koh EK, Song SH, Sung JE, Kim DS, Hong JT, Hwang DY (2016) Neuroprotective effects of fermented soybean products (Cheonggukjang) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on trimethyltin-induced cognitive defects mice. Nutr Neurosci 19(6):247-259. doi: 10.1179/1476830515Y.0000000025 PMID: 25923962

Objective: This study aimed to investigate the beneficial effects of Cheonggukjang (CGK) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on neurotoxic damages.

Summary: The short- and long-term memory loss induced by trimethyltin (TMT) treatment was significantly improved in the CGK-pretreated group in a dose-dependent manner. A dose-dependent increase in nerve growth factor (NGF) concentration, activation of the NGF receptor signaling pathway including the TrkA high affinity receptor and p75 NTR low affinity receptor was measured in all TMT/CGK-treated groups.

Usage: Western Blot

Related Products: NGFR (mu p75) Rabbit Polyclonal, affinity-purified (Cat. #AB-N01AP)

Arroyo D, Kirkby L, Feller M (2016) Retinal waves modulate an intraretinal circuit of intrinsically photosensitive retinal ganglion cells. J Neurosci 36:6892-6905. doi: 10.1523/JNEUROSCI.0572-16.2016 PMID: 27358448

Summary: The researchers explore the neural circuits underlying the ipRGC driven light responses of the developing retina and the mechanisms by which retinal waves regulate these circuits. They demonstrate that, even in the presence of cholinergic waves, ipRGC gap junction microcircuits propagate light-driven signals, thus strongly contributing to the overall light response of the developing retina. Following fixation, retinas were washed in PBS and remounted onto a new piece of filter paper. They were incubated in blocking buffer and then in primary immunoreaction solution, 1:2500 rabbit anti-melanopsin (Cat. #AB-N38). Results show that, during development, ipRGCs form extensive gap junction microcircuits that shape the early retinal light response. Retinal waves exert a far-reaching, neuromodulatory influence on these circuits via dopaminergic modulation of gap junctions, thus potentially impacting the processing of early visual input.

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Mimura S, Suga M, Okada K, Kinehara M, Nikawa H, Furue M (2016) Bone morphogenetic protein 4 promotes craniofacial neural crest induction from human pluripotent stem cells. Int J Dev Biol 60:21-28. doi: 10.1387/ijdb.160040mk PMID: 26934293

Usage: Immunocytochemistry and flow cytometry

Related Products: NGFr (ME20.4, p75) Mouse Monoclonal (Cat. #AB-N07)

Matsuura T, Kawasaki M, Hashimoto H, Yoshimura M, Motojima Y, Saito R, Ueno H, Maruyama T, Ishikura T, Sabanai K, Mori T, Ohnishi H, Onaka T, Sakai A, Ueta Y (2016) Possible involvement of the rat hypothalamo-neurohypophysial/-spinal oxytocinergic pathways in acute nociceptive responses. J Neuroendocrinol 28(6) doi: 10.1111/jne.12396

Summary: It has been suggested that the amplification of GABAergic neurons in the inhibitory system induces the selective inhibition by Oxytocin (OXT) of excitability in the spinal cord, and the pain transmitted from the periphery to the dorsal horn of the spinal cord by this action may be attenuated at the spinal cord level. Rats were injected IT with Oxytocin-SAP (Cat. #IT-46) dissolved in saline (0.06 μg/μl), Blank-SAP (Cat. #IT-21) dissolved in saline (0.06 μg/μl), or saline. Formalin-induced acute nociception activated OXT-containing cells in both the magnocellular and parvocellular divisions of hypothalamus, and that the parvocellular division remains activated longer than the magnocellular division. Acute nociception-induced activation of the hypothalamo-neurohypophysial system caused elevation of plasma OXT levels. In addition, the OXTergic spinal pathway may be involved in pain modulation via OXTRs in the spinal cord.

Related Products: Oxytocin-SAP (Cat. #IT-46), Blank-SAP (Cat. #IT-21)