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)

Jin H, Li M, Jeong E, Castro-Martinez F, Zuker CS (2024) A body–brain circuit that regulates body inflammatory responses. Nature 630(8017):695-703. doi: 10.1038/s41586-024-07469-y PMID: 38692285

Objective: To show that a peripheral immune insult strongly activates the body–brain axis to regulate immune responses.

Summary: Using Anti-DBH-SAP, the authors demonstrate that pro-inflammatory and anti-inflammatory cytokines communicate with distinct populations of vagal neurons to inform the brain of an emerging inflammatory response. In turn, the brain tightly modulates the course of the peripheral immune response. Genetic silencing of this body–brain circuit produced unregulated and out-of-control inflammatory responses. By contrast activating this circuit affords neural control of immune responses.

Usage: Bilateral injection into the caudal nucleus of the solitary tract of mice with Anti-DBH–SAP (IT-03, 20 ng per side).

Related Products: Anti-DBH-SAP (Cat. #IT-03)

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)

Smakosz A, Matkowski A, Nawrot-Hadzik I (2024) Phytochemistry and biological activities of agrostemma genus-a review. Plants (Basel) 13(12):1673. doi: 10.3390/plants13121673 PMID: 38931105

Objective: In this review, papers focused on the chemical composition and bioactivity of the two accepted species of the Agrostemma genus were examined.

Summary: A vast amount of data exists about the cytotoxicity of Agrostemma and other Caryophyllaceae plants. However, there are huge differences between models and experimental procedures, resulting in difficulty in reaching reasonable conclusions as to whether or not these properties would indeed be pharmacologically relevant for anti-cancer therapies.

Usage: Saporin inhibits HIV-1 reverse transcriptase, HIV-1 protease, and HIV-1 integrase (Au et al.). Saponins isolated from a related plant—Gypsophila sp. —enhanced the cytotoxicity of saporin 100,000-fold. This demonstrates how important the synergy of RIPs and saponins is in the toxicity of plants from Caryophyllaceae (Hebestreit et al.)

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

See Also:

• Au, T.K.; Collins, R.A.; Lam, T.L.; Ng, T.B.; Fong, W.P.; Wan, D.C.C. The Plant Ribosome Inactivating Proteins Luffin and SaporinAre Potent Inhibitors of HIV-1 Integrase.FEBS Lett.2000,471, 169–172.
• Hebestreit, P.; Weng, A.; Bachran, C.; Fuchs, H.; Melzig, M.F. Enhancement of Cytotoxicity of Lectins by Saponinum Album.Toxicon2006,47, 330–335.

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 450:109070. 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.