References

Kumawat C, Takahashi T, Date I, Tomita Y, Tanaka M, Arataki S, Komatsubara T, Flores AOP, Yu D, Jain M (2024) State-of-the-art and new treatment approaches for spinal cord tumors. Cancers (Basel) 16(13):2360. doi: 10.3390/cancers16132360 PMID: 39001422

Objective: To discuss innovative approaches in treating spinal cord tumors.

Summary: Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body’s own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach.

Usage: A notable study by Yan et al. involved a novel bone-targeted protein nanomedicine that combines saporin with a boronated polymer, encapsulated in an anionic poly (aspartic acid) layer. In mouse models, these nanoparticles accumulated in the bone and released saporin in response to the acidic tumor environment, effectively inactivating ribosomes and inducing cancer cell death.

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

See Also:

• Yan Y et al. Targeted and intracellular delivery of protein therapeutics by a boronated polymer for the treatment of bone tumors. Bioact Mater 7:333-340, 2021.

Garaudé S (2024) Engineering an antibody-discernible and functional CD45 variant on hematopoietic stem and progenitor cells via base editing. Univ Basel Thesis.

Objective: To develop a system for a cell surface marker present on all hematopoietic cell to deplete malignant cells. Authors screened CD45’s extracellular domain regions with base editors and generated multiple CD45 protein variants altering the binding of antibodies.

Summary: Authors selected the CD45 K352E/G variant profile and improved its base editing rate as it showcased loss of binding of a unique anti-CD45 antibody while still maintaining the surface marker’s expression, stability, and function in human hematopoietic stem and progenitor cells (HSPCs). The resulting loss of antibody binding prompted the modification and humanization of the anti-CD45 antibody, culminating in the development of an anti-CD45 antibody-drug conjugate (CD45-ADC; CIM053-SG3376). In an AML mouse models xenografted with HSPCs, administration of the CD45-ADC selectively depleted human leukemia and HSPCs wt cells while preserving the healthy hematopoietic system derived from the transplanted base edited HSPCs.

Usage: In vitro antibody-drug-conjugate (ADC) mediated killing assays. For ADC killing assays involving saporin, a 100 nM stock was prepared by incubating the biotinylated antibody and Streptavidin-ZAP at a 1:1 molar ratio for 30 min at room temperature

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

Kiyokawa Y, Ootaki M, Kambe Y, Tanaka KD, Kimura G, Tanikawa T, Takeuchi Y (2024) Approach/avoidance behavior to novel objects is correlated with the serotonergic and dopaminergic systems in the brown rat (rattus norvegicus). Neuroscience 549:110-120. doi: 10.1016/j.neuroscience.2024.05.003 PMID: 38723837

Objective: To compare the dopaminergic, serotonergic, and noradrenergic systems immunohistochemically among rats.

Summary: The serotonergic system suppresses avoidance behavior, while the dopaminergic system enhances approach behavior to novel objects.

Usage: Immunohistochemistry (1:5000) Anti‐CRH antibody (AB‐02).

Related Products: Corticotropin Releasing Hormone Rabbit Polyclonal (Cat. #AB-02)

Shirsat SD, Londhe PV, Gaikwad AP, Rizwan M, Laha SS, Khot VM, Achal C, Tabish TA, Thorat ND (2024) Endosomal escape in magnetic nanostructures: Recent advances and future perspectives. Materials Today Advances 22:100484. doi: 10.1016/j.mtadv.2024.100484

Objective: To investigate the use of magnetic nanoparticles (MNPs) as functional nano-objects to enhance the therapeutic effects by disrupting or rupturing the endocytic vesicles in terms of endosomal escape.

Summary: When MNPs are functionalized for cancer therapy, the endosomal escape agent should break the endosomal membrane when it fuses with lysosomes, i.e. late endosomes, which are highly acidic and comprised of large amounts of hydrolytic enzymes, which additionally contribute to cytotoxic effects. However, when MNPs are used for gene delivery, endosomal release from early endosomes should be desirable because it is less toxic than late endosomes, thus increasing the biocompatibility and promoting healthy growth and gene expression in targeted cells.

Usage: Saporin is mentioned as an endosomal escape agent.

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

See Also:

• Vago R et al. Saporin and ricin A chain follow different intracellular routes to enter the cytosol of intoxicated cells. FEBS J 272(19):4983-4995, 2005.

Garaudé S, Marone R, Lepore R, Devaux A, Beerlage A, Seyres D, Dell’ Aglio A, Juskevicius D, Zuin J, Burgold T, Wang S, Katta V, Manquen G, Li Y, Larrue C, Camus A, Durzynska I, Wellinger LC, Kirby I, Van Berkel PH, Kunz C, Tamburini J, Bertoni F, Widmer CC, Tsai SQ, Simonetta F, Urlinger S, Jeker LT (2024) Selective haematological cancer eradication with preserved haematopoiesis. Nature 630(8017):728-735. doi: 10.1038/s41586-024-07456-3 PMID: 38778101

Objective: To demonstrate that an antibody–drug conjugate (ADC) targeting the pan-haematopoietic marker CD45 enables the antigen-specifc depletion of the entire haematopoietic system, including Haematopoietic stem cells ( HSC).

Summary: Pairing this ADC with the transplantation of human HSCs engineered to be shielded from the CD45-targeting ADC enables the selective eradication of leukaemic cells with preserved haematopoiesis. The combination of CD45-targeting ADCs and engineered HSCs creates an almost universal strategy to replace a diseased haematopoietic system, irrespective of disease aetiology or originating cell type.

Usage: For ADC killing assays involving saporin, a 100 nM stock was prepared by incubating the biotinylated antibody (BC8 or MIRG451 mAbs) and saporin–streptavidin (IT-27) at a 1:1 molar ratio for 30 min at room temperature

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

Barioni NO, Beduschi RS, da Silva AV, Martins MG, Almeida-Francia CCD, Rodrigues SA, López DE, Gómez-Nieto R, Horta-Júnior JAC (2024) The role of the ventral nucleus of the trapezoid body in the auditory prepulse inhibition of the acoustic startle reflex. Hearing Research doi: 10.1016/j.heares.2024.109070 PMID: 38972084

Objective: To study the acoustic startle response through elimination of the ventral nucleus of the trapezoid body neurons via Anti-ChAT-SAP injection.

Summary: The elimination of ventral nucleus of the trapezoid body (VNTB) is used while measuring the auditory prepulse inhibition and acoustic startle response with and without this group of neurons to study their role in rats. It was found The VNTB stands as the sole identified source of cholinergic inputs to Cochlear root neurons.

Usage: Lesions in the VNTB were performed via a bilateral microinjection of a neurotoxin selective for cholinergic neurons, the anti-ChAT-saporin (IT-42, 0.25 ug/μl, 400 nL)

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Simpson J, Starke CE, Ortiz AM, Ransier A, Darko S, Llewellyn-Lacey S, Fennessey CM, Keele BF, Douek DC, Price DA, Brenchley JM (2024) Immunotoxin-mediated depletion of Gag-specific CD8+ T cells undermines natural control of Simian immunodeficiency virus. JCI Insight e174168. doi: 10.1172/jci.insight.174168 PMID: 38885329

Objective: To investigate the role of gag epitope-specific CD8+ T cells in the immune control of Simian Immunodeficiency Virus (SIV) in a nonhuman primate model.

Summary: Antibody-mediated depletion studies suggest that CD8+ T cells suppress SIV replication, but bulk depletion of CD8+ T cells may increase SIV target cells. Authors selectively depleted CD8+ T cells specific to the CM9 epitope, but this didn’t suppress viral replication in SIV-infected rhesus macaques. The data indicate that CM9-specific CD8+ T cells alone are not sufficient for immune control of SIV.

Usage: Streptavidin-ZAP was added stepwise to purified CM9 monomers to a final molar ratio of 1:4 and administered intravenously at a doses of 350 pmol/kg, 500 pmol/kg, 1 nmol/kg, or 2 nmol/kg at various time intervals.

Related Products: Streptavidin-ZAP (Cat. #IT-27)

See Also:

• Hess PR et al. Selective deletion of antigen-specific CD8+ T cells by MHC class I tetramers coupled to the type I ribosome-inactivating protein saporin. Blood 109:3300-3307, 2007.
• Leitman EM et al. Saporin-conjugated tetramers identify efficacious anti-HIV CD8+ T-cell specificities. PLoS One. 2017;12(10):e0184496.

Collins HM, Greenfield S (2024) Rodent models of alzheimer’s disease: Past misconceptions and future prospects. Int J Mol Sci 25(11):6222. doi: 10.3390/ijms25116222 PMID: 38892408

Objective: To outline the various apparent causes of Alzheimer’s Disease (AD) and evaluate the success or otherwise of their reproduction in rodents.

Summary: To understand the pathogenesis of AD and how it progresses through the brain, the authors describe the need of an animal model that reproduces the causal mechanism driving the disease. For decades, researchers have attempted to model AD by recapitulating downstream markers of its pathology, including cholinergic neuron loss, Aβ and tau aggregation, and neuroinflammation. Insights gained from the study of Parkinson’s Disease (PD) show that we must model the actual neurodegenerative mechanisms of AD in adult, wildtype animals by specifically targeting the neural populations first affected by a disease. The authors propose an alternative model, based on the aberrant accumulation of the novel peptide T14. In the review, specific cholinergic neuron degeneration was produced by 192 IgG-saporin, which resulted in degeneration of cholinergic cell bodies and terminals via apoptotic cell death.

See Also:

• Book AA et al. 192 IgG-saporin: I. Specific lethality for cholinergic neurons in the basal forebrain of the rat. J Neuropathol Exp Neurol 53:95-102, 1994.
• McGaughy J et al. The role of cortical cholinergic afferent projections in cognition: impact of new selective immunotoxins. Behav Brain Res 115:251-263, 2000.
• Holley LA et al. Cortical cholinergic deafferentation following the intracortical infusion of 192-IgG-saporin: a quantitative histochemical study. Brain Res 663:277-286, 1994.

Nishioka M, Hata T (2024) Cholinergic interneurons in the dorsal striatum play an important role in the acquisition of duration memory. Eur J Neurosci 59(11):3061-3073. doi: 10.1111/ejn.16337 PMID: 38576223

Objective: To investigate duration-memory formation in the dorsal striatum.

Summary: Rats were sufficiently trained using a peak-interval 20s procedure and then infused with anti-choline acetyltransferase–saporin into the dorsal striatum to cause selective ablation of cholinergic interneurons. Lesions of the cholinergic cells show delayed memory acquisition and suggest dorsal striatum neurons play a role in new duration memory.

Usage: Each group of rats received aCSF or anti-choline acetyltransferase (ChAT)–saporin (Anti-ChAT-SAP, IT-42) at 0.5 μg/μL at 0.5 μl/min for 2 mins.

Related Products: Anti-ChAT-SAP (Cat. #IT-42)

Nirogi R, Jayarajan P, Benade V, Abraham R, Goyal VK (2024) Hits and misses with animal models of narcolepsy and the implications for drug discovery. Expert Opin Drug Discov 19(6):755-768. doi: 10.1080/17460441.2024.2354293 PMID: 38747534

Objective: To review the usage of Orexin-B-SAP treated rats in the development of drug candidates for the treatment of narcolepsy.

Summary: Examines pharmacological agents used for the modeling of narcolepsy in animals and contrasts it with narcolepsy expression in real patients. Additionally summarizes the discovery of the orexin system in narcolepsy and how animal models aided in that discovery.

Usage: Orexin- B-saporin (IT-20) was injected into the lateral hypothalamus of rats.

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