2013 Targeting Trends Review

Tuscano JM, Kato J, Pearson D, Xiong C, Newell L, Ma Y, Gandara DR, O’Donnell RT (2012) CD22 antigen is broadly expressed on lung cancer cells and is a target for antibody-based therapy. Cancer Res 72(21):5556-5565. doi: 10.1158/0008-5472.CAN-12-0173

Summary: The median overall survival of patients with advanced, unresectable, non-small cell lung cancer is 9-12 mos. A potential therapeutic target is CD22, a protein expressed on lung cancer cells. The authors examined the use of the monoclonal antibody HB22.7 as an antitumor agent. To assess internalization of the antibody, it was first incubated with 10 μg/ml Mab-ZAP (Cat. #IT-04) then applied to two different cancer cell lines in culture. Analysis of cell viability demonstrated that CD22 internalized when bound by the antibody-toxin complex, suggesting that targeting CD22 has therapeutic potential.

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

Vetrivelan R, Fuller PM, Yokota S, Lu J, Saper CB (2012) Metabolic effects of chronic sleep restriction in rats. Sleep 35(11):1511-1520. doi: 10.5665/sleep.2200

Summary: In order to investigate whether there is a correlation between sleep and weight the authors administered 200 nl of a 0.1% solution of orexin-SAP (Cat. #IT-20) to the ventrolateral preoptic area of rats. Although the lesioned animals slept less than the controls, weight gain was slower than controls.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Daniels-Wells TR, Helguera G, Rodriguez JA, Leoh LS, Erb MA, Diamante G, Casero D, Pellegrini M, Martinez-Maza O, Penichet ML (2013) Insights into the mechanism of cell death induced by saporin delivered into cancer cells by an antibody fusion protein targeting the transferrin receptor 1. Toxicol In Vitro 27(1):220-231. doi: 10.1016/j.tiv.2012.10.006

Summary: The antibody-avidin fusion protein ch128.1Av has been shown to target the human transferrin receptor 1 (TfR1) and kill malignant B cells by blocking the use of iron. Combination of this construct with a mono-biotinylated saporin custom conjugate produces an iron-independent toxicity to TfR1-expressing cells, even those that are resistant to ch128.1Av alone. The saporin-containing conjugate induces a transcriptional response consistent with oxidative stress and DNA damage. The data also show that the saporin conjugate is not toxic to human hematopoeietic stem cells.

Usage: An antibody-avidin fusion protein (ch128.1Av) was mixed with MonoBiotin-ZAP to make an immunotoxin that targets the human transferrin receptor 1 (TfR1).

Related Products: MonoBiotin-ZAP (Cat. #BT-ZAP), Custom Conjugates

Kato J, Satake N, O’Donnell RT, Abuhay M, Lewis C, Tuscano JM (2013) Efficacy of a CD22-targeted antibody-saporin conjugate in a xenograft model of precursor-B cell acute lymphoblastic leukemia. Leuk Res 37(1):83-88. doi: 10.1016/j.leukres.2012.09.010

Summary: Most cases of acute lymphoblastic leukemia (ALL) are of B-cell lineage. Although children with ALL have a high survival rate, there is a subset of children with a much lower survival rate, and long-term side effects from treatment are problematic. CD22 has been suggested as a therapeutic target because it is not present on hematopoietic stem cells, therefore allowing regeneration of normal B cells following depletion of malignant B cells. The authors used a custom conjugate of the antibody HB22.7 and saporin to demonstrate specific toxicity against pre-B ALL cell lines. Mouse IgG-SAP (Cat. #IT-18) was used as a control.

Related Products: Mouse IgG-SAP (Cat. #IT-18), Custom Conjugates

Croxson PL, Browning PG, Gaffan D, Baxter MG (2012) Acetylcholine facilitates recovery of episodic memory after brain damage. J Neurosci 32(40):13787-13795. doi: 10.1523/JNEUROSCI.2947-12.2012

Summary: Episodic memory is controlled by several interconnected brain structures. The order in which these structures sustain damage can affect the processes lost. In this work the authors performed numerous bilateral injections of ME20.4-SAP (Cat. #IT-15) into the infero-temporal cortex, the medial surface of the temporal lobe, the perirhinal and entorhinal cortex, and the temporal pole of monkeys. These injections totaled 2.2-2.5 μg of conjugate. The results indicate that loss of cortical acetylcholine function will interfere with adaptation to memory impairments caused by structural damage in episodic memory centers.

Related Products: ME20.4-SAP (Cat. #IT-15)

Babalola PA, Fitz NF, Gibbs RB, Flaherty PT, Li PK, Johnson DA (2012) The effect of the steroid sulfatase inhibitor (p-O-sulfamoyl)-tetradecanoyl tyramine (DU-14) on learning and memory in rats with selective lesion of septal-hippocampal cholinergic tract. Neurobiol Learn Mem 98(3):303-310. doi: 10.1016/j.nlm.2012.09.003

Summary: Steroid sulfatase inhibitors such as dehydroepiandrosterone (DHEAS) have memory-enhancing effects. Working with both DHEAS and the steroid sulfatase inhibitor DU-14, the authors examined cholinergic function by infusing 0.2 μg of 192-IgG-SAP (Cat. #IT-01) into the medial septum of rats. The results indicate that memory associated with contextual fear is facilitated by steroid sulfatase inhibition, but acquisition of spatial memory is impaired by these same lesions.

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

Estevez ME, Fogerson PM, Ilardi MC, Borghuis BG, Chan E, Weng S, Auferkorte ON, Demb JB, Berson DM (2012) Form and function of the M4 cell, an intrinsically photosensitive retinal ganglion cell type contributing to geniculocortical vision. J Neurosci 32(39):13608-13620. doi: 10.1523/JNEUROSCI.1422-12.2012 PMID: 23015450

Summary: Intrinsically photosensitive retinal ganglion cells (ipRGCs) are cells that contain the photopigment melanopsin. In this work the authors extensively characterize the M4 ipRGCs. A melanopsin antibody (Cat. #AB-N38) at a 1:10,000 dilution was used to determine the presence of melanopsin by immunohistochemistry.

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

Zant JC, Rozov S, Wigren HK, Panula P, Porkka-Heiskanen T (2012) Histamine release in the basal forebrain mediates cortical activation through cholinergic neurons. J Neurosci 32(38):13244-13254. doi: 10.1523/JNEUROSCI.5933-11.2012

Summary: The basal forebrain modulates many functions, among them the regulation of wakefulness and cortical arousal. Previous data has linked increases in histaminergic transmission to increases in wakefulness. In order to further investigate various facets of this system, the authors injected 230 ng of 192-IgG-SAP (Cat. #IT-01) into the horizontal diagonal band of Broca/substantia innominata/magnocellular preoptic area of rats. While control animals displayed several changes on administration of exogenous histamine, the lesioned animals had none of these changes.

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

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)

Alvarez P, Chen X, Bogen O, Green PG, Levine JD (2012) IB4(+) nociceptors mediate persistent muscle pain induced by GDNF. J Neurophysiol 108(9):2545-2553. doi: 10.1152/jn.00576.2012

Summary: GDNF is found in skeletal muscle and can trigger mechanical hyperalgesia. The authors administered a 3.2-μg intrathecal dose of IB4-SAP (Cat. #IT-10) to rats. Loss of the IB4(+) nociceptors led to decreased hyperalgesic priming as well as a reduction in GDNF-induced hyperalgesia. These data indicate that GDNF plays a role in mediating induction of pain.

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