References

Crees ZD, DiPersio JF, Persaud SP (2026) Making space for cures: conditioning for autologous hematopoietic stem cell gene therapies. Seminars in Hematology doi: 10.1053/j.seminhematol.2026.09.001

Objective: To define the role transplant conditioning regimens play in autologous gene therapy, including contrasting the goals of care in this setting with those for stem cell transplantation for malignancies.

Summary: The phosphatase CD45 and the tyrosine kinase CD117 are the most frequently targeted antigens in HSCT conditioning studies. CD45-SAP and CD117-SAP were both highly effective at depleting murine HSCs, enabling transplantation between major histocompatibility complex

Related Products: Streptavidin-ZAP (Cat. #IT-27), Anti-CD117-SAP (Cat. #IT-83), Anti-CD45.2-SAP (Cat. #IT-91)

See Also:

• Czechowicz A et al. Selective hematopoietic stem cell ablation using CD117-antibody-drug-conjugates enables safe and effective transplantation with immunity preservation. Nat Commun 10:617, 2019.
• Palchaudhuri R et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol 34:738-745, 2016.

Yaksh T, Hayek SM (2026) Historical perspective on evolution of neuraxial delivery for pain (1975-2025). Reg Anesth Pain Med 51(9):1012-1027. doi: 10.1136/rapm-2026-108095 PMID: 42710949

Objective: To consider the historical trajectory that reflects the evolution of neuraxial therapeutics that has transpired over the last 50 or so years, with a particular emphasis on its application to pain and its management. The review addresses the advances that led to where we are now in the 21st century with neuraxially targeted therapeutics and consideration of where this thread leads.

Summary: Strategies include toxins such as saporin or exotoxins linked to Substance P allowing selective depletion of neurokinin-1 receptor-expressing dorsal horn projection neurons activated by polymodal C fibers. At present, resiniferatoxin and SP saporin are in first-in-human phase I dose- escalation clinical trial.

Related Products: Saporin (Cat. #PR-01), SP-SAP (Cat. #IT-07)

Ouyang R, Fan X, Wang X, Tan S, Wei M, Huo Y, Li H (2026) Selective intrinsically photosensitive retinal ganglion cells ablation regulates myopia development through the choroid/MAPK pathway. Curr Eye Res 1-13. doi: 10.1080/02713683.2026.2715205 PMID: 42606289

Objective: To investigate the role of selective ablation of intrinsically photosensitive retinal ganglion cells (ipRGCs) in regulating axial length and scleral remodeling during myopia progression.

Summary: Results revealed that the ipRGCs mediate the effects of choroid/MAPK pathway on axial length, providing a refined understanding of retinal mechanisms and identifying a potential therapeutic target for myopia

Usage: Three-week-old pigmented guinea pigs received intravitreal Melanopsin-SAP (IT-44) injections

Related Products: Melanopsin-SAP (Cat. #IT-44)

Wang H, Zhang L, Ye C, Li X, Sun M (2026) Intestinal epithelial ion channel TMEM16A deficiency impairs enteroendocrine cell differentiation and epithelial homeostasis and enhances anxiety-like behavior in mice. J Army Med Univ 48(15):2151-2163. doi: 10.16016/j.2097-0927.202605055

Objective: To investigate the effects of intestinal epithelial transmembrane member 16A (TMEM16A) deficiency on the differentiation phenotype of chromogranin A (CgA)-positive EECs, related gut-brain signaling molecules, hippocampal inflammatory signals and anxiety-like behavior, and to analyze the role of the vagal afferent pathway in this process

Summary: Intestinal epithelial TMEM16A deficiency attenuates the differentiation phenotype of CgA+ EECs, reduces 5-HT, TPH1, GLP-1 and PYY levels, and is accompanied by enhanced NLRP3/IL-1β inflammatory signals in the hippocampal CA3 region and anxiety-like behavior. The CCK-sensitive vagal afferent pathway is involved in TMEM16A deficiency-related anxiety-like behavior.

Usage: The wild type and knockout mice were treated with CCK-SAP (IT-31) or Blank-SAP (IT-21). Immunohistochemical staining and Western blotting were performed to detect the expression of intestinal epithelial renewal-related molecules and those in inflammatory signals in the hippocampal CA3 region.

Related Products: CCK-SAP (Cat. #IT-31), Blank-SAP (Cat. #IT-21)

Navarre S, Ishibashi MN, Nair A, Reyes-Torres I, Belabed M, Halasz L, Park MD, Mattiuz R, Ounadjela M, Gunset G, Mansilla-Soto J, Feucht J, Cabriolu A, Le Berichel J, Birbrair A, Eyquem J, Brown BD, Merad M, Sadelain M, Ahmed J (2026) Tumor irradiation promotes antigen dressing of dendritic cells to enhance CAR T cell persistence and efficacy in lung metastases. Nat Cancer 7(7):1104-1120. doi: 10.1038/s43018-026-01167-6 PMID: 42174275

Objective: To investigate strategies to selectively enhance CAR T cell activity at tumor sites to widen the therapeutic window.

Summary: Using syngeneic models of extensive metastatic lung adenocarcinoma and melanoma, the authors showed irradiation increased CAR T cell numbers within tumors but not in adjacent normal lung tissue that also expressed target antigen, conferring robust control of tumor without increased toxicity.

Usage: CD117 was combined with Streptavidin-ZAP (IT-27) and administered at 1 mg  kg−1 per recipient to selectively deplete host hematopoietic stem and progenitor cells. In vivo administration of immunotoxin was performed by i.v. injections (300 μl).

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

Dib C, Queenan JA, Willner H, Swartzrock L, Charlesworth CT, Denis M, Davis JR, Mepani RJ, Ho K, Castro M, Wilson RC, Nakauchi H, Liu DR, Czechowicz A (2026) Restoration of the immune system with base editing and non-genotoxic conditioning in a Rag2 point-mutant mouse model. Mol Ther 34(7):4070-4083. doi: 10.1016/j.ymthe.2026.04.010 PMID: 41968583

Objective: To investigate therapy that would eliminate the risks associated with current hematopoietic stem cell (HSC) gene-modification and conditioning approaches.

Summary: The authors combined base editors, engineered virus-like particles, and non-genotoxic CD117-SAP conditioning to explore optimal curative treatment of severe combined immunodeficiency. Results showcased a significant advancement in reducing treatment-related toxicities while enabling disease correction.

Usage: Using a mouse model, Anti-CD117 was combined with Streptavidin-ZAP (IT-27) and administered at 1.5 mg/kg via intravenous injection 8 days before transplantation.

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

Chen Q, Sahbaie P, Irvine KA, Clark JD (2026) Persistent headache and pain sensitization after traumatic brain injury is driven by mu-opioid receptor-positive neurons in the rostral ventromedial medulla for both males and females. Research Square doi: 10.21203/rs.3.rs-9890815/v1

Objective: To investigate whether mu-opioid receptor-positive (Oprm+) pain-facilitating neurons are essential for posttraumatic pain behaviors, ongoing vulnerability to postsurgical and headache-like pain, and latent pain sensitization after mild traumatic brain injury in both male and female animals.

Summary: The rostral ventromedial medulla (RVM) is a key output node of the endogenous pain modulation system, which contains mu-opioid receptor-positive (Oprm+) pain-facilitating neurons that are important in chronic pain. Periorbital mechanical sensitivity was used as a headache-related measure, and hindpaw mechanical withdrawal thresholds were used to assess distal pain sensitization. Lesioning these neurons abolished BLS-induced reinstatement of periorbital allodynia at 5 and 9 weeks after injury in both males and females.

Usage: Male and female C57BL/6J mice received microinjection of Dermorphin-SAP (IT-12)) to lesion RMV Oprm+ neurons, or Blank-SAP (IT-21) as controls (1.5 picomoles in 300 nL of phosphate-buffered saline).

Related Products: Dermorphin-SAP / MOR-SAP (Cat. #IT-12), Blank-SAP (Cat. #IT-21)

Okalova J, Alexander JS, Patel SR, Branella GM, Barichello de Quevedo C, Baldwin WH, Prince C, Chandrakasan S, Brown HC, Doering CB, Spencer HT (2026) Antimetabolites synergize with antibody drug conjugate-based non-genotoxic conditioning facilitating hematopoietic stem cell-directed lentiviral gene therapy. Mol Ther Adv doi: 10.1016/j.omta.2026.201780

Objective: To investigate the hypothesis that anti-CD117-sap is not effective as a single non-genotoxic conditioning agent in hematopoietic stem and progenitor cells (HSPCs)-directed lentiviral vector gene therapy for hemophilia A due to a lack of deep HSPC depletion in the bone marrow (BM).

Summary: The authors demonstrated how conditioning with non-genotoxic conditioning ADCs, such as Anti-CD117-SAP, causes cycling of residual HSPCs in the BM niche. There is potential of repurposing antimetabolites into these non-genotoxic conditioning regimens when combined with immune suppression to further target ADC-induced cycling HSPCs and augment depletion in the BM prior to HSCT.

Usage: A conjugate with Streptavidin-Saporin and biotinylated CD117 was developed. Mice were conditioned with the conjugate at doses ranging from 0.5 to 1 mg/kg.

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

Tierno Lauer L, Hayes AMR, Suarez AN, Bashaw A, Klug ME, Kao AE, Cheng R, Rea JJ, Subramanian KS, Nourbash A, Donohue KN, Schier LA, Myers K, Décarie-Spain L, Kanoski SE (2026) The vagus nerve promotes memory in rats via nutrient-induced septo-hippocampal acetylcholine signaling. Nat Commun doi: 10.1038/s41467-026-73896-2 PMID: 42236727

Objective: To demonstrate that nutrient consumption promotes hippocampal-dependent memory function via vagus nerve-mediated acetylcholine (ACh) release in the dorsal hippocampus (HPCd) from medial septum (MS) neurons

Summary: Recent findings highlight a role for vagus nerve-mediated gut-brain signaling in regulating higher-order cognitive processes. MS cholinergic neuron ablation, subdiaphragmatic vagotomy, and Western Diet impaired memory for meal location, suggesting that this signaling pathway functions to promote memories for eating events. Collectively, results identify a neurobiological mechanism whereby nutrient consumption enhances memory function and suggest that disruption of this vagal-brain signaling system mediates WD-associated memory impairments.

Usage: Rats were injected with either a 192-IgG-SAP (IT-01) in the MS (to ablate MS cholinergic neurons) or a control saporin (PR-01).

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

Gupta S, Kesler MT, Scantlebury MH, Sloviter RS, Teskey GC (2026) Modeling temporal lobe epilepsy with hippocampal sclerosis in rats using the selective neurotoxin stable substance P-saporin. Epilepsia doi: 10.1002/epi.70322 PMID: 42220243

Objective: To determine the time course of SSP-­SAP-­induced epileptogenesis, as well as the loss of principal cells and astrogliosis, two defining features of Temporal lobe epilepsy with hippocampal sclerosis (TLE-­ HS+)

Summary: Temporal lobe epilepsy with hippocampal sclerosis (TLE-­ HS+) is a common and often refractory form of human epilepsy. SSP-­SAP was internalized within 2 h after injection and was immunocytochemically undetectable by 5 days. Rats exhibited spontaneous electrographic and behavioral reactive seizures between days 4 and 6 after SSP-­SAP injection, with most seizures having a Racine score of either 1 or 2. This study confirms that the SSP-­ SAP model reproduces the defining features of human TLE and that a primary, selective, and longitudinally extensive γ- aminobutyric acidergic defect is sufficient to trigger epileptogenesis that results in TLE-­HS+.

Usage: 150 nL of SSP-SAP (0.04 ng/nL, IT-11) was injected at a rate of 1 nL/s into four unilateral sites along the longitudinal axis of the rat dentate gyrus. To determine the time course for SSP-­ SAP internalization (n=4), rats were perfused at 2 h and 1, 3, and 5 days following SSP-­ SAP administration. Following coronal cryosectioning of the hippocampus, sections were placed in a 500-­μL solution of 1:350 Saporin Goat Polyclonal, affinity-purified Alexa 488 (AB-15AP-FLA) and .01 mol·L−1 PBS at room temperature overnight. Sections were inspected and imaged at 40× with 4× digital zoom using an Olympus Fluoview FV3000 confocal microscope.

Related Products: SSP-SAP (Cat. #IT-11), Saporin Goat Polyclonal, affinity-purified Alexa488-labeled (Cat. #AB-15AP-FLA)