Tolymbekova A, Lezina L (2025) CD320 receptor and vitamin B12 as potential targets for anti-cancer therapy. Int J Mol Sci 26(12):5652. doi: 10.3390/ijms26125652 PMID: 40565117
Objective: To develop therapies discriminating between healthy and cancerous cells to prevent unwanted toxicity of anticancer agents.
Summary: One possible method is to target proteins overexpressed in cancer but not in normal cells. CD320 is a receptor responsible for the uptake of the transcobalamin-bound fraction of vitamin B12 (cobalamin), which is necessary for DNA synthesis, and thus, cell proliferation. CD320 was shown to be overexpressed in many cancers and its potential role as an early cancer biomarker was confirmed in several studies.
Usage: In CD320-overexpressing HEK293 cells, a 2.5 nM concentration of monoclonal antibodies conjugated with saporin was enough to induce a 100% inhibition of proliferation, while in normal HEK293 cells, the same concentration of antibodies induced approximately 50% inhibition of cell proliferation.
Zhu M, Wu Y, Gao H, Qi F, Zhang X, Ran Y (2025) Differential regulation of mTOR activity in retinal ganglion cells underlies their distinct susceptibility to ischemia/reperfusion. Commun Biol 8(1):911. doi: 10.1038/s42003-025-08314-2 PMID: 40500296
Objective: To explore why intrinsically photosensitive retinal ganglion cells (ipRGCs) are more resistant to ischemia/reperfusion (I/R) injury than other RGC subtypes and to examine the role of mTOR signaling in this differential vulnerability.
Summary: ipRGCs exhibited higher mTOR activity and greater resistance to I/R injury compared to other RGCs. Rapamycin had cell-type–specific effects: it protected non-ipRGCs by increasing mTOR activity but suppressed mTOR in ipRGCs unless light was removed, revealing that light conditions critically influence mTOR-mediated neuroprotection.
Usage: Melanopsin (OPN4) was detected using Anti-Melanopsin (AB-N39) at a 1:2000 dilution to identify and quantify ipRGCs in retinal whole-mounts following ischemic injury.
Ren X, Wang Y, Zhang Y (2025) Targeted depletion of dysfunctional hematopoietic stem cells mitigates myeloid-biased differentiation in aged mice. Cell Discov 11:56. doi: 10.1038/s41421-025-00810-3 PMID: 40490480
Objective: To develop and evaluate a targeted strategy for depleting dysfunctional, myeloid-biased CD150-high hematopoietic stem cells (HSCs) in aged mice to restore balanced hematopoiesis and mitigate aging-related blood disorders.
Summary: The study used an antibody-toxin conjugate to selectively eliminate CD150-high HSCs, improving lymphoid-to-myeloid ratios, reducing platelet hyperproduction, and restoring hematopoietic balance in aged mice. Treatment preserved functional CD150-low HSCs and showed minimal off-target or systemic toxicity.
Usage: Streptavidin-ZAP (IT-27) was combined with a biotinylated anti-CD150 antibody to generate Anti-CD150-SAP (IT-103). This conjugate was used at doses of 1–2 mg/kg in vivo and as low as 0.01 nM in vitro to specifically deplete CD150-high HSCs while sparing CD150-low populations.
Movahed AY, Bagheri R, Savatier P, Šarić T, Moradi S (2025) Elimination of tumorigenic pluripotent stem cells from their differentiated cell therapy products: An important step toward ensuring safe cell therapy. Stem Cell Reports 102543. doi: 10.1016/j.stemcr.2025.102543 PMID: 40541178
Objective: To review and evaluate current strategies for eliminating tumorigenic pluripotent stem cells (PSCs) from differentiated cell therapy products to improve the safety of PSC-based regenerative therapies.
Summary: Residual undifferentiated PSCs pose a tumorigenic risk in cell therapies. This review outlines genetic, antibody, toxin, and small molecule strategies for selectively removing PSCs, emphasizing the need for efficient, selective methods to ensure safety in regenerative medicine.
Usage: References a previous study that used Fab-ZAP to eliminate pluripotent stem cells by targeting specific surface markers, demonstrating its application as a targeted immunotoxin for PSC depletion.
Zhang Z, He F, Li W, Liu B, Deng C, Qin X (2025) Material-driven therapeutics: Functional nanomaterial design paradigms revolutionizing osteosarcoma treatment. J Funct Biomater 16(6):213. doi: 10.3390/jfb16060213 PMID: 40558899
Objective: To examine nanomaterial applications in Osteosarcoma (OS) therapy through a materials science lens, analyzing mechanism specific interventions. The analysis establishes a framework for developing next-generation nanotherapeutic platforms to address persistent limitations in OS management.
Summary: Phytic acid (PA)-functionalized nanoparticles (e.g., MnO2-PA) exploit high hydroxyapatite affinity for osseous tumor accumulation. Bone-specific targeting is exemplified by saporin-boronated nanotherapeutics, which achieve ribosomal inactivation through hydroxyapatite binding, offering a targeted approach for bone malignancies.
Usage: Saporin delivery in an orthotopic model significantly inhibited Osteosarcoma. GPSP (100 μg/kg saporin + 133.3 μg/kg GP + 140 μg/kg PASP) was intravenously injected with a Saporin concentration of 100 µg/kg. In a Bone-Metastatic Breast Cancer disease model, GPSP (150 μg/kg saporin + 200 μg/kg GP + 210 μg/kg PASP) was injected with a Saporin concentration of 150 µg/kg.
Son S, Beaudoin DL, Hassan AR, Akpo MS, Ichinose T, Garrett AM (2025) A characterization of mouse retinal ganglion cell types labeled with AAV tools. bioRxiv 2025.06.02.657062. doi: 10.1101/2025.06.02.657062
Objective: To characterize the cell-type specificity and functional diversity of retinal ganglion cells (RGCs) labeled by AAV vectors carrying synthetic promoters ProA13 and ProA27 in the mouse retina.
Summary: ProA13 and ProA27 AAV vectors selectively labeled molecularly and morphologically distinct subsets of RGCs, including melanopsin-positive ipRGC subtypes. ProA27 labeled a broader diversity of ipRGCs (M1–M4), while ProA13 primarily labeled M1 cells, enabling analysis of their structural, functional, and projection differences.
Usage: Melanopsin (OPN4) was detected using Anti-Melanopsin (AB-N38) at a 1:5000 dilution to identify and classify ipRGCs in AAV-labeled retinas.
Konturek-Ciesla A, Zhang Q, Kharazi S, Bryder D (2025) A non-genotoxic stem cell therapy boosts lymphopoiesis and averts age-related blood diseases in mice. Nat Commun 16(1):5129. doi: 10.1038/s41467-025-60464-3 PMID: 40456713
Objective: Application of Hematopoietic stem cell (HSC) transplantation leads to treatment toxicity. Therefore, authors employed a murine transplantation model based on low-intensity conditioning protocols using antibody-mediated HSC depletion to improve hematopoietic output and ameliorate age-compromised lymphopoiesis.
Summary: Authors demonstrate that young HSCs, once effectively engrafted in aged hosts, improve hematopoietic output and ameliorate age-compromised lymphopoiesis. This culminated in a strategy that robustly mitigates disease progression in a genetic model of myelodysplastic syndrome. These results suggest that non-genotoxic HSC transplantation could fundamentally change the clinical management of age-associated hematological disorders, offering a prophylactic tool to delay or even prevent their onset in elderly patients.
Usage: CD45-SAP (3 mg/kg) was administered to young (2 months) and aged (16 months) C57BL/6-CD45.2 mice
Anderson KL (2025) Neural mechanisms of context-sensitive behavior in the adult male zebra finch. City Univ NY Thesis.
Objective: To test whether oxytocin and dopamine mediate the influence of the social behavior network on the vocal control network in songbirds, enabling context-dependent changes to song.
Summary: The study reveals direct anatomical links between hypothalamic nodes of the social behavior network and the vocal control network. Blocking oxytocin receptors disrupts appropriate female-directed song and correlated network activity.
Usage: To assess brain access and persistence of intranasal compounds, Oxytocin-SAP (IT-46) was delivered intranasally at 1 μg/ml (12 μL total, 0.0012 mg per bird).
Chauhan P, Hu S, Sheng WS, Prasad S, Lokensgard JR (2025) bTRM control of murine cytomegalovirus cns reactivation. 26(11):5275. doi: 10.3390/ijms26115275 PMID: 40508083
Objective: To determine the role of CD8+ and CD103+ brain-resident memory T cells (bTRMs) in controlling murine cytomegalovirus (MCMV) reactivation in the central nervous system.
Summary: Depleting CD103+ bTRMs led to transient viral gene expression and delayed recovery of infectious virus from explants, implicating these cells in maintaining latency. bTRM depletion also triggered expression of disease-associated microglial genes, suggesting a role in modulating neuroimmune responses.
Usage: Anti-CD103-SAP (IT-50) was injected intracerebroventricularly (2 µg) to selectively deplete CD103+ bTRMs in latently infected mice. This targeted depletion achieved ~90% T-cell reduction and was critical for assessing viral reactivation and microglial activation phenotypes.
McLeod CM, Son S, Haque MN, Garrett AM (2025) Reduced neuronal self-avoidance in mouse starburst amacrine cells with only one Pcdhg isoform. bioRxiv 2025.05.29.656828. doi: 10.1101/2025.05.29.656828 PMID: 40502005
Objective: To determine whether the γC4 isoform of the protocadherin-γ (Pcdhg) gene cluster is sufficient to mediate neuronal self-avoidance in starburst amacrine cells (SACs) in the mouse retina.
Summary: While deletion of γC4 or γC5 alone did not impair SAC self-avoidance, mice expressing only γC4 exhibited significant failures in dendritic self-avoidance that were not fully rescued by transgenic overexpression. These findings suggest γC4 is specialized for neuronal survival but insufficient to support self-avoidance on its own.
Usage: Melanopsin (OPN4) was detected using Anti-Melanopsin (AB-N38) at a 1:2000 dilution to label intrinsically photosensitive retinal ganglion cells (ipRGCs) for analysis of retinal cell spacing and mosaic organization.
