targeted-toxins

Leanza MH, Storelli E, D’Arco D, de Leo G, Kleiner G, Arancio L, Capodieci G, Gulino R, Bava A, Leanza G (2025) Cerebellar contributions to spatial learning and memory: Effects of discrete immunotoxic lesions. Int J Mol Sci 26(19):9553. doi: 10.3390/ijms26199553 PMID: 41096819

Objective: To analyze the behavioral and anatomical effects of discrete injections, in different groups of animals, of the same 192 IgG-saporin toxin into the basal forebrain nuclei and/or into the cerebellar vermis and hemispheres.

Summary: Authors administered, 192 IgG-saporin, selectively targeting cholinergic neurons in the basal forebrain and a subpopulation of cerebellar Purkinje cells, to adult rats bilaterally into the basal forebrain nuclei, the cerebellar cortices or both areas combined. The results suggest important functional interactions between the ascending regulatory inputs from the cerebellum and those arising in the basal forebrain nuclei that would act together to modulate the complex sensory–motor and cognitive processes required to control whole body movement in space.

Usage: (i) bilateral intraventricular injection of 192 IgG-saporin (ICV, n = 12); (ii) bilateral injections of 192 IgG-saporin into the basal forebrain nuclei (BF, n = 12); (iii) injections of 192 IgG-saporin into the cerebellar hemispheres and vermis (CBL, n = 12); and (iv) injections of 192 IgG-saporin into both the basal forebrain nuclei and cerebellar hemispheres and vermis (BF/CBL, n = 12).

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

Herrerias A, Oliverio A, Dvorácskó S, Thyagarajan A, Chedester L, Liu J, Cinar R, Iyer MR, Kunos G, Godlewski G (2026) CB1 receptors on a subset of vagal afferent neurons modulate voluntary ethanol intake in mice. Mol Psychiatry 31(1):48-61. doi: 10.1038/s41380-025-03266-9 PMID: 40975751

Objective: To investigate how peripheral CB1 receptors on vagal afferent neurons regulate voluntary ethanol intake and their role in gut-brain signaling underlying alcohol consumption.

Summary: Selective deletion or ablation of CB1R in nodose ganglion neurons abolished the inhibitory effects of peripheral CB1R antagonists on voluntary ethanol intake. The study identifies CB1R on Gpr65⁺ vagal sensory neurons as critical mediators of gut-brain communication regulating alcohol preference and intake.

Usage: Anti-CB1-SAP (IT-104) or Blank-SAP (IT-21) was injected into the proximity of the nodose ganglion at 250 ng/mL to selectively ablate CB1R-expressing vagal afferent neurons

Related Products: Anti-CB1-SAP (Cat. #IT-104), Blank-SAP (Cat. #IT-21)

Kobayashi K, Miyazaki Y, Sakamoto N, Yamamoto M, Nagat N, Murata T (2025) Long-term scratching analysis of mice using machine learning. PNAS Nexus 4(9):pgaf292. doi: 10.1093/pnasnexus/pgaf292 PMID: 41030291

Objective: To objectively quantify mouse scratching behavior across light and dark cycles using automated, long-term machine learning analysis.

Summary: Naïve BALB/c mice exhibited more frequent and persistent scratching during the light period, and DNFB-induced dermatitis caused biphasic, long-lasting scratching even during rest. The study establishes a continuous behavior analysis method that reveals circadian and pathological pruritus features.

Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally at 400 ng in 5 μL PBS.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Alampi MM, Kozlíková M, Mariangeli M, Civita S, Delcanale P, Mussini A, Diaspro A, Bianchini P, Weyergang A, Skarpen E, Berg K, Viappiani C, Abbruzzetti S, Selbo PK (2025) Light-enhanced cytotoxicity and intracellular trafficking of the PD-L1-targeting photoimmunoconjugate EITC-atezolizumab. Biomed Pharmacother 191:118550. doi: 10.1016/j.biopha.2025.118550 PMID: 40946581

Objective: To optimize the cytotoxic efficacy of a photoimmunoconjugate of eosin-5-isothiocyanate and atezolizumab (EITC-atezolizumab) in NSCLC cells; To study the uptake and intracellular transport of atezolizumab; and to evaluate EITC-atezolizumab as a candidate for photochemical internalization (PCI) of the ribosome-inactivating protein gelonin.

Summary: This is the first documentation demonstrating that atezolizumab is transported to CD63-positive organelles, thereby enhancing our understanding of its intracellular trafficking. The study also strengthens the concept of Photoimmunotherapy (PIT) and atezolizumab-based targeting of PD-L1+NSCLCs.

Usage: The cytotoxic efficacy of the PD-L1-targeting immunotoxin (Anti-PD-L1-SAP) was strongly enhanced in PD-L1-positive breast cancer cells by photochemical internalization (PCI),a low-dose, Photodynamictherapy (PDT)-based intracellular drug delivery method.

Related Products: Anti-PD-L1-SAP (Cat. #IT-45)

Hor CC (2025) The dual nature of cold: Unraveling the neural circuits for cool sensing and cold allodynia. Univ Michigan Thesis.

Objective: To elucidate the neural mechanisms underlying innocuous cool sensation from the skin to the brain and the spinal circuitry changes that drive cold allodynia under pathological conditions.

Summary: The study identified distinct spinal interneuron populations mediating innocuous cool sensation (Trhr⁺ neurons) and cold allodynia (Tac1⁺/Calb1⁺ neurons). Ablation of these neurons demonstrated their modality-specific contributions, with Trhr⁺ interneurons responsible for cool detection and Tac1⁺/Calb1⁺ neurons for pathological cold hypersensitivity, revealing a spinal circuit basis for temperature discrimination and pain plasticity.

Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally at a single dose of 400 ng in 10 µL sterile saline to ablate spinal GRPR⁺ neurons involved in thermal and itch processing.

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)

Lipari NR (2025) Investigating anxiety-like behaviors and basolateral amygdala dysfunction in a novel rat model of Parkinson’s disease. SUNY Binghamton Thesis.

Objective: To create a unique model of PD with improved face validity, and non-motor symptoms.

Summary: This work helped further characterize motor and non-motor symptoms while providing potential underlying physiological markers for early disease course in a unique animal model of Parkinson’s disease (PD).

Usage: It has been demonstrated that lesioning of the basolateral amygdala with the targeted toxin stable substance P (SSP) saporin, a toxin that selectively lesions neurons which express neurokinin1 receptors, increases anxiety-like behaviors in rats.

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

See Also:

• Truitt WA et al. Anxiety-like behavior is modulated by a discrete subpopulation of interneurons in the basolateral amygdala. Neuroscience 160:284-294, 2009.

Handfield J (2025) Focal irradiation regulates distal neural stem and progenitor cell behaviour. Univ Toronto Thesis.

Objective: To investigate how focal irradiation (IR) impacts non-irradiated neural stem cell (NSC) niches along the neuraxis and whether microglia mediate these long-distance effects.

Summary: Focal cranial IR decreased spinal cord-derived NSCs, while spinal IR reduced neuroblasts and NSCs in the forebrain. Microglia ablation did not rescue these effects, suggesting IR alters NSC behavior along the neuraxis independently of microglia.

Usage: Mac-1-SAP (CD11b, Cat. #IT-06) was cited as a method previously used for microglia ablation.

Related Products: Mac-1-SAP mouse/human (Cat. #IT-06)

See Also:

• Ribeiro Xavier et al. A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone. J Neurosci. 2015 Aug 26;35(34):11848-61. doi: 10.1523/JNEUROSCI.1217-15.2015. PMID: 26311768; PMCID: PMC4549398.

Diamantoudis SC, Miliotou AN, Galatou E, Telliou S, Sideris K, Grigoriadis N, Vizirianakis IS (2025) Assessing the hematological cancer stem cell landscape to improve immunotherapy clinical decisions. Biocell 49(10):1799-1858. doi: 10.32604/biocell.2025.067216

Objective: To combine existing information and clinical evidence to assess and bring to the spotlight targets related to Hematological cancer stem cells (HCSCs) that can be considered for the improvement of therapeutic interventions.

Summary: Targeting HCSCs represents one of the most promising advances toward achieving lasting remission and potential cure in hematologic malignancies. Next-generation immunotherapies—enabled by advances in molecular profiling, synthetic biology, and systems immunology—can shift the paradigm in blood cancers by overcoming current limitations.

Usage: CD117-ADC (carrying streptavidin–saporin) has shown dose-dependent results in mice, with a range from 0.3–1.5 mg/kg, as depletion of stem cells was noted with the subsequent successful engraftment of allogenic transplants.

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83)

Yuan M, Zhang L, Zhu H, Xie M (2025) Alteration of BDNF and noradrenergic markers in locus coeruleus in a mouse model of cancer-induced bone pain. PLoS One 20(8):e0330207. doi: 10.1371/journal.pone.0330207 PMID: 40811566

Objective: To examine the expression and localization of BDNF and NE neuron-specific proteins in the locus coeruleus (LC) of mice with cancer-induced bone pain (CIBP).

Summary: CIBP mice exhibited enhanced neuronal activity in the LC, upregulation of noradrenergic markers, and BDNF/TrkB-mediated modulation of noradrenergic neurons. Concurrently, inhibitory signalling was attenuated in the spinal dorsal horn (SDH).

Usage: Selective ablation of noradrenergic neurons via intracerebroventricular anti-DBH-SAP (IT-03) administration reduces mechanical and cold allodynia, suggesting that LC-spinal cord pathway activity is critical for pain modulation.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

See Also:

• Taylor BK, Westlund KN (2017) The noradrenergic locus coeruleus as a chronic pain generator. J Neurosci Res 95(6):1336-1346. doi: 10.1002/jnr.23956 PMID: 27685982

Noh M, Corrigan KA, Williams SG, Peirs C, Leone MJ, Headrick DJ, Guvercin M, Lee S, Phan BN, Yeramosu D, Babu S, Brown AR, Van De Weerd R, Zhao X, Dunn RP, Mathys H, Pfenning AR, Seal RP (2025) A molecular and spinal circuit basis for the functional segregation of itch and pain. bioRxiv 2025.07.31.667966. doi: 10.1101/2025.07.31.667966 PMID: 40766363

Objective: To define how distinct subtypes of Grpr⁺ dorsal horn neurons contribute to itch and pain processing and to demonstrate the utility of genomic enhancer-based strategies for modality-specific targeting.

Summary: The study revealed two functionally distinct Grpr⁺ neuron subtypes: Tac1⁻ neurons mediate itch, while Tac1⁺ neurons mediate mechanical allodynia. Selective silencing or ablation of each subtype modulated only its respective sensory behavior, illustrating clear modality segregation within the dorsal horn circuitry.

Usage: Bombesin-SAP (IT-40) or Blank-SAP (IT-21) was administered intrathecally (300 ng) to selectively ablate Grpr⁺ neurons

Related Products: Bombesin-SAP (Cat. #IT-40), Blank-SAP (Cat. #IT-21)