Cox TO, Devason AS, de Araujo A, Mason S, Subramanian M, Salvador AFM, Descamps HC, Kim J, Zhu Y, Litichevskiy L, Jung S, Song WS, Cortés-Martín A, Henderson NT, Huang KP, Nguyen T, Sae-Lee W, Umana IC, Sacta M, Rahman RJ, Wisser S, Nelson JAD, Golynker I, McSween AM, Hohmann EF, Patel S, Bub AL, Soekler C, Blank N, Hoxha K, Boccia L, Wong AC, Bahnsen K, Kim J, Biderman N, Abbasian D, Shoffler C, Petucci C, McAllister FE, Alhadeff AL, Fuccillo MV, Hill C, Jang C, Betley JN, de Lartigue G, Lee VY, Levy M, Thaiss CA (2026) Intestinal interoceptive dysfunction drives age-associated cognitive decline. Nature 652(8109):442-450. doi: 10.1038/s41586-026-10191-6 PMID: 41813891
Objective: To identify a mechanism by which inhibition of gut–brain signalling during ageing results in impaired neuronal activation in the hippocampus and loss of memory encoding.
Summary: The gastrointestinal microbiome has recently emerged as an important factor in the regulation of cognition and has been implicated as a modifiable peripheral signal that may contribute to age-associated memory loss. However, the circuits by which gut microbial signals are transmitted to the brain to modulate memory remain largely unclear. The authors evaluated CCKAR+ neurons to determine their role in cognitive decline.
Usage: CCK–SAP (IT-31) or Blank-SAP (IT-21) was injected (125 ng in 0.5 μl per ganglion).
Kozlíková M, Aukrust IKF, Rohlíčková M, Macháček M, Berg K, Weyergang A, Selbo PK (2026) Photochemical enhancement of PD-L1-SAP immunotoxin efficacy in non-small cell lung cancer cell lines. Front Immunol 17:1750003. doi: 10.3389/fimmu.2026.1750003 PMID: 41909645
Objective: To investigate photochemical internalization (PCI), a light–controlled endosomal escape technology, as a strategy to enhance intracellular delivery and efficacy of a PD–L1–targeted immunotoxin (anti–PD–L1–SAP).
Summary: Non–small cell lung cancer (NSCLC) cell lines with high (NCI–H1975) and low (A549) PD–L1 expression were subjected to PCI, resulting in a pronounced increase in cytotoxicity with picomolar potency (30 pM), while A549 cells required a higher dose (1000 pM) for a similar effect. PCI enhances delivery and activity of PD–L1–targeted biologics and may help overcome resistance mechanisms. Overall, PCI expands the therapeutic window of PD–L1–targeted immunotoxins and may complement current immunotherapies, supporting further preclinical evaluation in NSCLC.
Usage: Cells were then incubated with TPCS2a and anti-PD-L1-SAP (IT-45) for 18 h. The concentration of anti-PD-L1-SAP was 30, 100 and 1000 pM for NCI-H1975 cell line and 1000 pM for A549 cell line. BIgG-SAP (IT-74) was used as control.
Xiang H, Mortenson GP, Lang SB, Jakkaraju S, Chirala A, Zhu Y, Jia M, Wen J, Chen Y, Baghela A, Chen YC, Sze MA, Hegde LG, Zhang-Hoover J, Willingham A, Handa M, Chi A, Baltus GA, Kamath RV, Levesque M, Vollmann EH (2026) uPAR-targeting cytotoxic antibody–drug conjugates selectively deplete proinflammatory myeloid cells for autoimmune indications. Cells 15(9):803. doi: 10.3390/cells15090803
Objective: To explore uPAR as a cell-surface marker to target and eliminate proinflammatory monocytes and macrophages using antibody–drug conjugates (ADCs).
Summary: Using recent scRNA-seq findings from RA patients, the authors identified the urokinase plasminogen activator receptor (uPAR), encoded by PLAUR, as a highly expressed cell surface marker on an inflammation-associated IL1B+ proinflammatory myeloid subset. an anti-uPAR mAb conjugated with monomethyl auristatin F (MMAF) was employed to demonstrate selective depletion of uPARhigh-expressing macrophages in a myeloid-rich rodent model.
Usage: Fab-ZAP rat (IT-55) was used to test the internalization capacity of anti-mouse uPAR mAbs. Saporin and Fab-IgG-ZAP were used as control.
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.
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
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.
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.
Kolahdouzan M, Ghazisaeidi S, Tu Y, Muley M, Gambeta E, Salter M (2025) Meningeal macrophages mask incision pain sensitization in male rats. Mol Pain 21. doi: 10.1177/17448069251383593 PMID: 40958149
Objective: To investigate whether CD206+macrophages in the meninges play a role in regulating nociception and pain hypersensitivity.
Summary: The results indicate that while CD206+ meningeal macrophages do not regulate basal nociception in naïve rats, they mask mechanical hypersensitivity in male rats after skin incision injury. Thus, we conclude that in a sex-dependent manner, CD206+ meningeal macrophages prevent the spread of pain hypersensitivity after a minor injury.
Usage: Rats were injected intrathecally (30 μl) with saline, CD206-Saporin (20 μg mannose-receptor antibody and 7 μg of Streptavidin-ZAP in 30 μl), or Rabbit-IgG-Saporin (control).
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
We are highlighting one of our saporin conjugates, Bombesin-SAP. A tool for depleting cells that express gastrin releasing peptide receptor (GRPR). Bombesin is a 14-amino acid peptide actually found in frog skin. The human equivalent GRP has been detected in itch pathways and plays a role in eating behaviors.
Their objective was to investigate the functional contributions of specific spinal dorsal horn neuron subtypes to cold and pain sensation using targeted ablation and optogenetic tools.
The authors were able to administer Bombesin-SAP (IT-40) or a control conjugate (Blank-SAP, IT-21) intrathecally to ablate GRPR-positive spinal neurons to assess their role in sensory behavior.
In their study, they identified Calb1+ spinal neurons as essential mediators of cool sensation in mice. Behavioral and physiological responses following targeted ablation revealed distinct sensory processing roles for various neuronal subtypes.
