targeted-toxins

Kuroda M, Komatsu N, Kosai A, Hamakubo T, Abe T (2025) Anti-EGFR antibody immunotoxins improve cytotoxic effects in the salivary gland cancer A253 cell line. 37(3):450-454. doi: 10.1016/j.ajoms.2024.11.003

Objective: To confirm the antitumor effects of IT-Cetuximab (IT-Cmab= saporin-conjugated anti-EGFR antibody), which is cetuximab conjugated with a toxin, targeting salivary gland cancers—a type of cancer with limited effective treatment options aside from surgery.

Summary: Cmab alone exhibited no cytotoxic effects, but IT-Cmab demonstrated concentration-dependent cytotoxic effects in A253 cells.

Usage: Cytotoxicity assay (@1.34pM to 4.2nM)

Related Products: Saporin (Cat. #PR-01)

Lin CCJ, Tian Y, Tanzi RE, Jorfi M (2024) Approaches for studying neuroimmune interactions in Alzheimer’s disease. Trends Immunol S1471-4906(24)00248-5. doi: 10.1016/j.it.2024.10.002 PMID: 39537528

Objective: To examine cutting-edge strategies – encompassing animal and cellular models – used to investigate the roles of peripheral immune cells in AD.

Summary: Recent studies using rodent models and innovative human-based cellular systems are beginning to shed light on how peripheral immune cells infiltrate the brain and modulate disease progression.

Usage: Strategies for bone marrow depletion using anti-CD45 or anti-CD117 antibodies conjugated with the ribosome-inactivating protein saporin have been used.

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

See Also:

• 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.
• 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.

Moreno-Rodríguez M, Martínez-Gardeazabal J, Bengoetxea de Tena I, Llorente-Ovejero A, Lombardero L, González de San Román E, Giménez-Llort L, Manuel I, Rodríguez-Puertas R (2024) Cognitive improvement via cortical cannabinoid receptors and choline-containing lipids. Br J Pharmacol 182(4):1038-1058. doi: 10.1111/bph.17381 PMID: 39489624

Objective: Authors hypothesized that activation of the endocannabinoid system may confer neuroprotection against cholinergic degeneration.

Summary: Degeneration, induced by 192-IgG-saporin, of baso-cortical cholinergic pathways resulted in memory deficits and decreased cortical levels of lysophosphatidylcholines (LPC). The cannabinoid agonist WIN55,212-2 restored cortical cholinergic transmission and LPC levels via activation of cannabinoid receptors. This activation altered cortical lipid homeostasis mainly by reducing sphingomyelins in lesioned animals. These modifications were crucial for memory recovery.

Usage: Basal forebrain cholinergic degeneration was induced following bilateral stereotaxic injection of 192IgG-saporin (130 ng/μl, IT-01) into the nucleus basalis magnocellularis (NBM).

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

Chuang KH, Zhou XA, Xia Y, Li z, Qian L, Eeles E, Ngiam G, Fripp J, Coulson EJ (2024) Cholinergic basal forebrain neurons regulate vascular dynamics and cerebrospinal fluid flux. bioRxiv 2024.08.25.609536. doi: 10.1101/2024.08.25.609536

Objective: To show that vascular-CSF coupling correlates with cortical cholinergic activity in non-demented aged humans.

Summary: Waste from the brain is cleared via a cerebrospinal fluid (CSF) exchange pathway. Problems in this pathway is suggested to underlie the pathogenesis of many brain conditions. Cerebrovascula oscillation that couples with pulsatile CSF inflow is suggested to drive the flow of fluid, however how this coupling is regulated in unlcear. The resultsfor the study suggest a neurovascular mechanism by which CSF/glymphatic flux is modulated by cholinergic neuronal activity, thereby providing a conceptual basis for the development of diagnostics and treatments for glymphatic dysfunction.

Usage: Injections of mu-p75-SAP (0.5 mg/ml, IT-16) or control Rabbit-IgG-SAP (0.5 mg/ml, IT-35) were performed into the border between the medial septum and ventral diagonal band. In the first study, the toxin was infused at a rate of 0.4 μl/min (1.5μl total volume), which resulted in a large amount of ablation. In the second study, the toxin concentration was reduced to 0.3 mg/ml to preserve more cholinergic neurons and was infused at a rate of 0.18μl/min (1.0μl total volume).

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)

Blanco T, Nakagawa H, Musayeva A, Krauthammer M, Singh RB, Narimatsu A, Ge H, Shoushtari SI, Dana R (2024) Acquired immunostimulatory phenotype of migratory CD103+ DCs promotes alloimmunity following corneal transplantation. JCI Insight 9(20):e182469. doi: 10.1172/jci.insight.182469 PMID: 39235864

Objective: To investigate the interaction between antigen-presenting cell subsets, specifically CD11b+ dendritic cells (DC2) and CD103+ dendritic cells (DC1),in the context of transplant immunity.

Summary: The findings highlight the critical role of CD103+ DC1 in modulating host alloimmune responses. In recipients with uninflamed corneal beds, migratory CD103+ DC1 exhibit a tolerogenic phenotype. These cells influence the immunogenic behavior of CD11b+ DC2 primarily through IL-10 production, suppressing alloreactive CD4+ Th1 cells via the PD-L1/PD-1 pathway and promoting Treg-mediated tolerance through αvβ8 integrin–activated TGF-β1. Together, these mechanisms contribute to improved graft survival.

Usage: In vivo depletion of CD103+ DC1: Recipient BALB/c or RAG-/- mice were administered 2.0 mg/kg of Anti-CD103-SAP (IT-50) intraperitoneally, or an equivalent dose of control conjugate (IgG-SAP).

Related Products: Anti-CD103-SAP (Cat. #IT-50), Rat IgG-SAP (Cat. #IT-17)

Jiang H, Cui H, Chen M, Li F, Shen X, Guo CJ, Hoekel GE, Zhu Y, Han L, Wu K, Holtzman MJ, Liu Q (2024) Divergent sensory pathways of sneezing and coughing. Cell 187(21):5981-5997. doi: 10.1016/j.cell.2024.08.009 PMID: 39243765

Objective: To study the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing.

Summary: Sneezing and coughing are frequently associated with allergies and respiratory viral infections and it’s assumed both involve common sensory receptors and neurotransmission mechanisms. The author’s work show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3−) mediates sneezing. Although this same population innervates the trachea, it does not mediate coughing, and instead, a distinct sensory population (somatostatin SST) mediates coughing but not sneezing. NMB-SAP was used to ablate neruomedin B (NMB) receptor expressing and nucleus tractus solitarius (NTS) neurons. Deletion of these neurons did not affect the coughing responses to Ly344864 and IL-31 (agonists to SST neurons) suggesting that NMB-sensitive NTS neurons do not mediate coughing.

Usage: Neuronal ablation by SST-saporin and NMB-saporin. SST-saporin was made by mixing biotin-labeled somatostatin and Streptavidin-ZAP (IT-27) at a 1:1 molar ratio at room temperature for 20 minutes. SST-Saporin (10 μM, 50 nL), NMB-saporin (#IT-70; 50 ng in 50 nL) or Blank-SAP (#IT-21; 10 μM in 50 nL or 50 ng in 50 nL) was injected into the NTS region.

Related Products: Streptavidin-ZAP (Cat. #IT-27), NMB-SAP (Cat. #IT-70), Blank-SAP (Cat. #IT-21)

Limonta P, Chiaramonte R, Casati L (2024) Unveiling the dynamic interplay between cancer stem cells and the tumor microenvironment in melanoma: Implications for novel therapeutic strategies. Cancers (Basel) 16(16):2861. doi: 10.3390/cancers16162861 PMID: 39199632

Objective: To review the bidirectional communication between melanoma cancer stem cells (CSCs) and the tumor microenvironment, highlighting its role in drug resistance and tumor relapse.

Summary: Melanoma CSCs evade immune surveillance and recruit immune cells with immunosuppressive and tumor-promoting properties, establishing a supportive microenvironment. They also transfer stemness and aggressive traits to neighboring non-CSCs, driving tumor progression and metastasis. Targeting these interactions may offer novel therapeutic strategies for combating melanoma.

Usage: This review publication highlights the usage of Anti-CD271-SAP and CD133-SAP in previous publications.

Related Products: ME20.4-SAP (Cat. #IT-15), Anti-CD133-SAP (Cat. #IT-82), Saporin (Cat. #PR-01)

See Also:

• Ngo M et al. Antibody therapy targeting CD47 and CD271 effectively suppresses melanoma metastasis in patient-derived xenografts. Cell Rep 16:1701-1716, 2016.
• Bostad M et al. Light-controlled endosomal escape of the novel CD133-targeting immunotoxin AC133-saporin by photochemical internalization – A minimally invasive cancer stem cell-targeting strategy. J Control Release 206:37-48, 2015.

Coutinho EA, Esparza LA, Steffen PH, Liaw R, Bolleddu S, Kauffman AS (2024) Selective depletion of kisspeptin neurons in the hypothalamic arcuate nucleus in early juvenile life reduces pubertal LH secretion and delays puberty onset in mice. FASEB J 28(19):e70078. doi: 10.1096/fj.202401696R PMID: 39377760

Objective: To investigate the specific kisspeptin population timing pubertal onset.

Summary: This study teases apart the contributions of different kisspeptin neural populations to the control of puberty onset, demonstrating that a majority of KNDy neurons in the arcuate nucleus are necessary for the proper timing of puberty in both sexes.

Usage: See also these studies where ~70% of ARC kisspeptin (KNDy) neurons were selectively ablated in rats using NKB-SAP (IT-63).

Related Products: NKB-SAP (Cat. #IT-63)

See Also:

• Mittelman-Smith MA et al. Arcuate kisspeptin/neurokinin b/dynorphin (KNDy) neurons mediate the estrogen suppression of gonadotropin secretion and body weight. Endocrinology 153(6):2800-2812 , 2012 .
• Helena C et al. KNDy neurons modulate the magnitude of the steroid-induced luteinizing hormone surges in ovariectomized rats. Endocrinology 156:4200-4213, 2015.
• Mittelman-Smith M et al. Ablation of KNDy neurons results in hypogonadotropic hypogonadism and amplifies the steroid-induced LH surge in female rats. Endocrinology 157:2015-2027, 2016.
• Campideli-Santana AC et al. Partial loss of arcuate kisspeptin neurons in female rats stimulates luteinizing hormone and decreases prolactin secretion induced by estradiol. J Neuroendocrinol 34(11):e13204, 2022.

Lusk S, Moushey AM, Li A, Ray R (2024) Exaggerated postnatal surge of orexin neurons and the effects of elimination of excess orexin on blood pressure and exaggerated chemoreflex in spontaneously hypertensive rats. Front Physiol 15:1341649. doi: 10.3389/fphys.2024.1341649 PMID: 39469444

Objective: To investigate whether an increase in postnatal neurogenesis of orexin (OX) neurons in spontaneously hypertensive rats (SHRs) precedes and contributes to elevated mean arterial pressure (MAP) and heightened responses to elevated CO2 (hypercapnia) during development.

Summary: Postnatal increase in OX neurons may be essential for the development of higher MAP and an exaggerated chemoreflex (the body’s response to CO2) in SHRs. Targeting the overactive OX system could provide a potential therapeutic strategy during the early stages of hypertension development.

Usage: Orexin-SAP (0.5 μL, 90 ng/μL) was injected into the hypothalamus to eliminate excess OX neurons and study their effect on elevated MAP and exaggerated chemoreflex responses in adult SHRs.

Related Products: Orexin-B-SAP (Cat. #IT-20)

Doucette L, Turnbill V, Carlin K, Cavanagh A, Sollinger B, Kuter N, Flock DL, Robinson S, Chavez-Valdez R, Jantzie L, Martin LJ, Northington FJ (2024) Neocortical cholinergic pathology after neonatal brain injury is increased by Alzheimer’s disease-related genes in mice. Neurobiol Dis 200:106629. doi: 10.1016/j.nbd.2024.106629 PMID: 39111704

Objective: Authors hypothesized that neocortical damage caused by neonatal Hypoxic-ischemic (HI) in mice is ushered by persistent cholinergic innervation and interneuron (IN) pathology that correlates with cognitive outcome and is exacerbated by genes linked to Alzheimer’s disease.

Summary: Simple ChAT+axonal swellings were present in all sham and HI groups; Tg mice had more than their nTg counterparts, but HI did not affect the number of axonal swellings. In contrast, complex ChAT+neuritic clusters (NC) occurred only in Tg mice. The abundance of ChAT+ clusters in specific regions correlated with decreased Visual discrimination. This finding aligns with data that a highly specific cholinergic immunotoxin (mu p75-SAP) in the APP/PS1 mouse model worsens cognitive impairment, and the cognitive impairment appears earlier

Related Products: mu p75-SAP (Cat. #IT-16)

See Also:

• Ramos-Rodriguez JJ et al. Rapid beta-amyloid deposition and cognitive impairment after cholinergic denervation in app/ps1 mice. J Neuropathol Exp Neurol 72(4):272-285, 2013.