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.
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.
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
Windhorst U, Dibaj P (2025) Nociception and acute pain: Neurotransmitters and neuromodulators. Preprints.org preprints202508.0487.v1. doi: 10.20944/preprints202508.0487.v1
Objective: To review the huge variety of additional neurotransmitters, neuromodulators and hormones in the nociceptive and pain system
Summary: Nociception and acute pain are governed by a dynamic interplay of structures and substances, modulated by internal and external factors, and vulnerable to pathological reorganization.
Usage: The injection of anti‐DBH‐SAP induced neurodegeneration restricted to the NA A5 cell group and confirmed by the decrease in the number of NA neurons only in the A5 group.
Nie AA, Taylor BK (2025) The pharmacotherapeutic potential of neuropeptide Y for chronic pain. J Intern Med 298(4):280-896. doi: 10.1111/joim.20118 PMID: 40754889
Objective: To evaluate how neuropeptide Y (NPY) and its receptor subtypes (Y1 and Y2) regulate acute and chronic pain, and to explore the therapeutic potential of targeting these pathways for the treatment of neuropathic and inflammatory pain.
Summary: The review highlights that spinal Y1-interneurons contribute to both sensory and affective components of chronic pain and that Y1 receptor activation can inhibit pronociceptive signaling. Prior studies using NPY-SAP demonstrated that ablation of Y1-expressing neurons reduces hypersensitivity in models of nerve injury and inflammation, supporting Y1 modulation as a therapeutic avenue.
Usage: NPY-SAP (IT-28) was referenced in the context of earlier studies employing intrathecal administration to ablate spinal Y1-interneurons.
Pandala N, De Melo Haefeli L, Lang M, Stone EM, Mullins RF, Tucker BA, Han IC (2025) Development of a targeted choroidal injury model for the study of retinal degenerations and therapeutic cell replacement. bioRxiv 2025.07.29.667466. doi: 10.1101/2025.07.29.667466 PMID: 40766580
Objective: To report a new targeted choroidal injury model using saporin conjugates and compare them to models of systemic sodium iodate administration.
Summary: Suprachoroidal administration of Anti-CD38-SAP or Anti-CD105-SAP resulted in severe choroidal vascular injury localized to the injection site, without damage to adjacent choroidal vasculature, progressive injury over time, or development of choroidal neovascularization. By contrast, sodium iodate treated animals had rapid, diffuse choroidal loss which progressed throughout the study time points, with fatal systemic side effects at the highest (75 mg/kg) dose.
Usage: Anti-CD38-SAP (IT-96) or Anti-CD105-SAP (IT-80) were diluted in sterile PBS at a concentration of 0.05 μg/μl. To induce selective choroidal cell injury, 10μl of saporin conjugate solution was delivered via suprachoroidal injection.
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.
Nazmuddin M, Stammes MA, Klink PC, Vernes MK, Bakker J, Langermans JAM, van Laar T, Philippens IHCHM (2026) Stereotactic lesioning of cholinergic cells by injection of ME20.4 Saporin in the nucleus basalis of Meynert in a rhesus monkey (Macaca mulatta). J Neuropathol Exp Neurol 85(1):58-70. doi: 10.1093/jnen/nlaf081 PMID: 40673943
Objective: To describe a procedure to inject ME20.4-SAP, an immunotoxin that specifically binds to and depletes cholinergic neurons stereotactically into the nucleus basalis of Meynert (NBM) of a rhesus monkey (Macaca mulatta).
Summary: A digital non-human primate brain atlas was co-registered to the brain of the monkey. A custom-designed cranial chamber was also implanted to the skull to guide the injection. The effects of the ME20.4-SAP injections were evaluated in vivo with PET-CT using [18F]-FEOBV as a radiotracer. This approach yielded reliable spatial accuracy and successful delivery of ME20.4-SAP into the NBM. This saporin-mediated selective destruction of cholinergic neurons in the NBM, using MRI-guidance and a cranial chamber, offers a promising method to study the pathophysiology of NBM degeneration and possible therapeutic interventions.
Usage: The first dose was chosen based on previous NBM lesioning works in common marmosets where infusing 1.4 μg ME20.4-SAP (Cat. #IT-15, in a concentration of 0.20 μg/μl) into each side of the NBM produced partial NBM depletion. At the second injection session, 5 μg ME20.4-SAP (in 0.5 μg/μl solution) was administered into each NBM side.
Nollet M, Ba W, Soto BA, Yin C, Lignos L, Jovic K, Vyssotski AL, Yustos R, Franks NP, Wisden W (2025) The selective amyloid-driven failure of cholinergic medial septal neurons in aging mice perturbs REM sleep, cognition and emotion, and broadcasts amyloid to other brain regions. bioRxiv 2025.07.09.663930. doi: 10.1101/2025.07.09.663930
Objective: To look genetically at the intersection of amyloid pathology and the cholinergic system in Alzheimer’s disease (AD).
Summary: The broadcasting of amyloid by medial septal cholinergic cells is a notable feature, and potentially important in human pathology, selective genetic lesioning of about one third of the medial septal cholinergic cells, independent of amyloid, gave the same REM sleep, cognitive and emotional phenotypes. Thus, it is the killing of the cholinergic cells by amyloid, and therefore the missing acetylcholine, and not the secreted/deposited amyloid in the hippocampus and other areas, that is the critical feature. These findings underscore the interest in revitalizing the classic cholinergic hypothesis of AD. Restricting pathological amyloid expression to MS cholinergic neurons, so that their health is compromised by amyloid, is sufficient to reproduce many AD-like symptoms, highlighting the critical role of these cells in early AD pathogenesis, REM sleep regulation, emotion and cognition.
Usage: Cholinergic neurons throughout the forebrain in mice were lesioned with mu p75-SAP. The loss of cholinergic innervation exacerbated neurovascular impairments and cerebral amyloid angiopathy progression in the cortex and hippocampus
Noble EE, Harris RBS (2025) Leptin in the VMH contributes to the initial overconsumption of palatable diets by rats. Am J Physiol Endocrinol Metab 329(1):E1-E17. doi: 10.1152/ajpendo.00090.2025 PMID: 40418155
Objective: To determine whether leptin receptor–expressing neurons in the ventromedial hypothalamus (VMH) contribute to the initial overconsumption of a high-fat diet in rats.
Summary: Ablation of VMH leptin receptor–expressing neurons using Leptin-SAP prevented the early hyperphagic response to a high-fat diet in male rats but had no long-term impact on energy intake, body weight, or glucose clearance. These findings suggest VMH leptin signaling plays a key role in initiating, but not maintaining, diet-induced hyperphagia.
Usage: Leptin-SAP (IT-47) or Blank-SAP (IT-21) was stereotaxically injected into the VMH of male and female rats (20 ng in 80 nL) to ablate leptin receptor–expressing neurons. This targeted lesion confirmed the role of VMH leptin signaling in mediating early-phase overeating in response to a high-fat diet.
