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Enhanced antitumor efficacy of a combination of immunotoxin and photosensitizer under illumination in xenograft mice
Hamakubo S, Komatsu N, Kosai A, Kuroda M, Sawada M, Shimizu R, Ohashi R, Suenaga H, Hamakubo T, Abe T (2026) Enhanced antitumor efficacy of a combination of immunotoxin and photosensitizer under illumination in xenograft mice. Biomedicines 14:573. doi: 10.3390/biomedicines14030573
Objective: To investigate the in vivo therapeutic efficacy of intelligent Targeted Antibody Phototherapy (iTAP), utilizing light as a spatiotemporal trigger to promote the cytoplasmic release of toxins.
Summary: The authors investigated the in vivo therapeutic efficacy of iTAP using an EGFR-targeted IT composed of cetuximab conjugated to saporin (IT-Cmab), administered in combination with the clinically used photodynamic therapy (PDT) photosensitizer NPe6, in a xenograft mouse model. Findings indicate that iTAP represents a promising therapeutic strategy for HNSCC.
Usage: Biotinylated Cmab was mixed with streptavidin-saporin (IT-Cmab). Mice received intraperitoneal IT-Cmab (0.5 mg/kg), followed 72 h later by intravenous NPe6 (5 mg/kg).
Related Products: Streptavidin-ZAP (Cat. #IT-27)
PACAP/PAC 1 modulates light-induced sleep via the ipRGC-VLPO pathway
Wang W, Zhang Y, Li L, Xu Y, Zhang W, Chen X, Wang X, Tong G, Zhang P (2026) PACAP/PAC 1 modulates light-induced sleep via the ipRGC-VLPO pathway. Biochem Biophys Res Commun 808:153462. doi: 10.1016/j.bbrc.2026.153462 PMID: 41702189
Objective: To investigate the mechanism of PACAP in ipRGC–VLPO light-induced sleep.
Summary: Partial ablation of ipRGCs by Melanopsin-SAP reduced light-induced sleep duration, whereas PACAP 1-38 administration reversed this effect, leading to an increase in REM sleep. After the partial destruction of ipRGCs through the intraocular injection of saporin (SAP), we continued to observe the effect of PACAP on light-induced sleep. The results showed that after the microdialysis injection of PACAP 1-38 into the VLPO of SAP mice, the light-induced sleep of the mice increased; specifically, REM sleep significantly increased. The results suggest that PACAP is involved in ipRGC–VLPO-mediated light-induced sleep.
Related Products: Melanopsin-SAP (Cat. #IT-44)
Next-generation anti-DLL3 radiopharmaceuticals targeting high-grade neuroendocrine lung and prostate cancers
Tendler S, De Gregorio R, Balderes P, Michel AL, Hoang TT, Bauer D, Tully KM, Korsen JA, Lorenz IC, Khan AG, Carter L, Vergnolle O, Lebedeva IV, Nyakatura EK, Bodei L, Morris MJ, Poirier JT, Rudin CM, Lewis JS (2026) Next-generation anti-DLL3 radiopharmaceuticals targeting high-grade neuroendocrine lung and prostate cancers. Proc Natl Acad Sci U S A 123(6):e2505785123. doi: 10.1073/pnas.2505785123 PMID: 41628333
Objective: To report on the development of anti-DLL3 radioimmunoconjugates for use as either a diagnostic imaging tracer or a therapeutic agent. Delta-like ligand 3 (DLL3) is a tumor-selective cell surface protein upregulated in high-grade neuroendocrine tumors, including small-cell lung cancer (SCLC) and neuroendocrine prostate cancer (NEPC).
Summary: The authors generated a panel of human monoclonal antibodies targeting human DLL3 by immunizing transgenic mice engineered with a human immunoglobulin repertoire. Six select candidates were reformatted as human IgG4 anti-DLL3 mAbs.
Usage: NCI-H82 cells were seeded in a 96-well plate and incubated with serial dilutions of tested antibodies, premixed with the Fab–ZAP (IT-48) for 72 h.
Related Products: Fab-ZAP mouse (Cat. #IT-48)
An AIEgen-based carrier enables efficient cytosolic delivery of bioactive proteins
Yang Y, Jia H, Yang L, He B, Zhang K, Liu H (2026) An AIEgen-based carrier enables efficient cytosolic delivery of bioactive proteins. Int J Nanomedicine 21:1-14. doi: 10.2147/IJN.S557672
Summary: The authors report a novel AIEgen (Aggregation-induced emission luminogen) -based carrier, MTPABP-Guided-Intracellular-Carrier (MAGIC), that achieves high efficiency in delivering native proteins into the cytosol. MAGIC efficiently delivered trypsin, RNase A, and saporin into the cytosol of mammalian cell lines while preserving their enzymatic or functional activity. The MAGIC delivery system holds significant promise for advancing the study of cellular physiology and enabling precise therapeutic interventions.
Usage: HeLa cells were treated with MTPABP/saporin complexes. Saporin concentration was 5 μg/mL. Free saporin served as a control.
Related Products: Saporin (Cat. #PR-01)
Gene therapy via CRISPR/Cas9-mediated Cxcr4 disease allele inactivation reverses leukopenia in WHIM mice
Gao JL, Li Z, Calderon-Perez R, Pavek A, Kim L, McDermott DH, Murphy PM (2026) Gene therapy via CRISPR/Cas9-mediated Cxcr4 disease allele inactivation reverses leukopenia in WHIM mice. J Clin Invest 136(5):e202073. doi: 10.1172/JCI202073 PMID: 41505207
Objective: To provide proof of principle that CRISPR/Cas9-mediated inactivation of the Cxcr4 disease allele, combined with nongenotoxic HSC- targeted conditioning, may offer a safe and effective gene therapy strategy generalizable to all WHIM-causing mutations.
Summary: Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is an immunodeficiency caused by autosomal dominant hyperfunctional mutations in chemokine receptor CXCR4 that promote panleukopenia due to BM retention. The authors modified their previous protocol by adding conditioning with a nongenotoxic CD117-targeted immunotoxin, CD117-antibody-saporin-conjugate.
Usage: Mice were injected i.v. with CD117-SAP.
Related Products: Anti-CD117-SAP (Cat. #IT-83)
Modelling Temporal Lobe Epilepsy with Sclerosis in the SSP-Saporin ‘Trojan Horse’ Model
Gupta S (2026) Modelling Temporal Lobe Epilepsy with Sclerosis in the SSP-Saporin ‘Trojan Horse’ Model. Univ Calgary Thesis.
Objective: To confirm that the SSP-SAP model reproduces the defining features of human TLE and that a primary and selective GABAergic defect is sufficient to trigger epileptogenesis that results in TLE-HS+.
Summary: The author hypothesized that intrahippocampal SSP-SAP administration will first cause rats to exhibit reactive behavioural seizures, followed by self-generated epileptiform activity that will develop into electrographic seizures. Rats will also develop TLE anatomically characterized by progressive principal cell loss and astrogliosis.
Usage: Rats were stereotaxically injected with 150 nL of SSP-SAP (IT-11, 0.04 ng/nL) at 4 sites in the hippocampus.
Related Products: SSP-SAP (Cat. #IT-11)
Lesion-remote astrocytes govern microglia-mediated white matter repair
McCallum S, Suresh KB, Islam TS, Tripathi MK, Saustad AW, Shelest O, Patil A, Lee D, Kwon B, Leitholf K, Yenokian I, Shaka SE, Beveridge CH, Manchandra P, Randolph CE, Meares GP, Dutta R, Plummer J, Calsavara VF, Kawaguchi R, Knott SRV, Chopra G, Burda JE (2026) Lesion-remote astrocytes govern microglia-mediated white matter repair. Nature 649(8098):959-970. doi: 10.1038/s41586-025-09887-y PMID: 41407858
Objective: To investigate Lesion-remote astrocytes (LRAs) from spared regions of mouse spinal cord following traumatic spinal cord injury.
Summary: The nature of astrocyte-extrinsic mechanisms that trigger discrete reactivity states are not well understood. Using Ccn1 expression as a biomarker of a molecularly distinct white matter LRA reactivity state, the authors explored the mechanism of its induction. IB4-SAP and CTB-SAP were injected in mice to selectively degenerate myelinated or non-myelinated sensory afferents, respectively.
Usage: 8 μg (10μl of 0.8 μg μl−1 in PBS) of Saporin (PR-01), IB4-SAP (IT-10) or CTB-SAP (IT-14) was injected subcutaneously into the plantar surface of the left hindpaw foot pad using a 30G insulin syringe.
Related Products: Saporin (Cat. #PR-01), IB4-SAP (Cat. #IT-10), CTB-SAP (Cat. #IT-14)
Summarizing the role of selected adipokines in parkinson’s disease: What is known about leptin, adiponectin, resistin, visfatin, and progranulin in neurodegeneration?
Milanowski J, Pawłowska M, Woźniak A, Szewczyk-Golec K (2025) Summarizing the role of selected adipokines in parkinson’s disease: What is known about leptin, adiponectin, resistin, visfatin, and progranulin in neurodegeneration?. Molecules 30(22):4431. doi: 10.3390/molecules30224431 PMID: 41302488
Objective: To summarize current evidence and identify potential targets for Parkinson’s disease (PD) treatment or as biomarkers of disease progression.
Summary: The improper secretion and function of leptin have been associated with carcinogenesis and obesity and have also been implicated in neurodegeneration and PD. The administration of Leptin-SAP, to eliminate cells that recognize and internalize leptin, thereby inducing cell ablation, resulted in an increase in anhedonia and signs of anxiety in the rats. However, the procedure did not affect the rats’ motor abilities. Injection led to a decrease in EWcp/UCN1 cells, suggesting neurodegeneration.
Related Products: Leptin-SAP (Cat. #IT-47)
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Electroacupuncture alleviates cognitive impairments in APP/PS1 mice via gastric vagal afferent-mediated activation of the nucleus tractus solitarius‒locus coeruleus noradrenergic circuit
Yu C, Li M, Shen F, Gao S, Wang J, He C, Wang L, Wu Y, Du Y (2025) Electroacupuncture alleviates cognitive impairments in APP/PS1 mice via gastric vagal afferent-mediated activation of the nucleus tractus solitarius‒locus coeruleus noradrenergic circuit. Chin Med 20(1):188. doi: 10.1186/s13020-025-01230-x PMID: 41233833
Objective: To demonstrate efficacy in ameliorating Alzheimer’s disease (AD)-related cognitive dysfunction through dual peripheral and central anti-infammatory actions using electroacupuncture (EA).
Summary: Transgenic mice were administrated with EA stimulation and cognitive function was assessed via the Morris water maze and novel object recognition tests. EA at ST36 and ST37 attenuated hippocampal synaptic ultrastructural degeneration. The experimental blockade of vagal aferent neurons via CCK-SAP injection into the nodose ganglion abolished the benefits induced by EA, directly implicating GVAF signaling in the improvement of EA-mediated AD.This intervention suppressed proinflammatory cytokines expression (IL-6, IL-1β, TNF-α) and microglial hyperactivation, effectively rescuing cognitive deficits in AD models.
Usage: CCK-SAP was injected into the nodose ganglion.
Related Products: CCK-SAP (Cat. #IT-31)
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Does amyotrophic lateral sclerosis (als) have metabolic causes from human evolution?
Spedding M (2025) Does amyotrophic lateral sclerosis (als) have metabolic causes from human evolution?. Cells 14(21):1734. doi: 10.3390/cells14211734 PMID: 41227379
Objective: To evaluate if recent human genetic variants play major roles in Amyotrophic Lateral Sclerosis (ALS), changing metabolism.
Summary: The authors reviewed Cholera Toxin B (CTB) binding as a tool to study GM1 and fucosylated structures, and to cause denervation. Findings suggest CTB may be used as a surrogate marker of GM1. CTB-SAP causes specific motor neuron death, presumably by binding to and downregulating GM1, and possibly other fucosylated targets; powerful evidence linking loss of GM1 to denervation in ALS.
Related Products: CTB-SAP (Cat. #IT-14)
See Also:
- Llewellyn-Smith IJ et al. Tracer-toxins: cholera toxin B-saporin as a model. J Neurosci Methods 103(1):83-90, 2000.
- Ciuro M et al. Mitigating the functional deficit after neurotoxic motoneuronal loss by an inhibitor of mitochondrial fission. Int J Mol Sci 25(13):7059, 2024.
- Gulino R et al. Neuromuscular plasticity in a mouse neurotoxic model of spinal motoneuronal loss. Int J Mol Sci 20(6):1500, 2019.
- Lind LA et al. Hypoglossal motor neuron death via intralingual CTB-saporin (CTB-SAP) injections mimic aspects of amyotrophic lateral sclerosis (ALS) related to dysphagia. Neuroscience 390:303-316, 2018.
- Lewis RD et al. Spinal TNF-α receptor 1 is differentially required for phrenic long-term facilitation (pLTF) over the course of motor neuron death in adult rats. Front Physiol 15, 2024.
- Chew C et al. Exercise is neuroprotective on the morphology of somatic motoneurons following the death of neighboring motoneurons via androgen action at the target muscle. Dev Neurobiol 81(1):22-35, 2021.
- Chew C et al. Exercise is neuroprotective on the morphology of somatic motoneurons following the death of neighboring motoneurons via androgen action at the target muscle. Dev Neurobiol 81(1):22-35, 2021.
- Lind LA et al. Tongue and hypoglossal morphology after intralingual cholera toxin B-saporin injection. Muscle Nerve 63(3):413-420, 2021.
- Keilhoz A et al. Tongue exercise ameliorates structural and functional upper airway deficits in a rodent model of hypoglossal motor neuron loss. Front Neurol 15:1441529, 2024.
