Tumor Evolution and Drug Response in Patient-Derived Organoid Models of Bladder Cancer.

Bladder cancer is the fifth most prevalent cancer in the U.S., yet is understudied, and few laboratory models exist that reflect the biology of the human disease. Here, we describe a biobank of patient-derived organoid lines that recapitulates the histopathological and molecular diversity of human bladder cancer. Organoid lines can be established efficiently from patient biopsies acquired before and after disease recurrence and are interconvertible with orthotopic xenografts. Notably, organoid lines often retain parental tumor heterogeneity and exhibit a spectrum of genomic changes that are consistent with tumor evolution in culture. Analyses of drug response using bladder tumor organoids show partial correlations with mutational profiles, as well as changes associated with treatment resistance, and specific responses can be validated using xenografts in vivo. Our studies indicate that patient-derived bladder tumor organoids represent a faithful model system for studying tumor evolution and treatment response in the context of precision cancer medicine.

Efficient and stable blue quantum dot light-emitting diode.

The visualization of accurate colour information using quantum dots has been explored for decades, and commercial products employing environmentally friendly materials are currently available as backlights1. However, next-generation electroluminescent displays based on quantum dots require the development of an efficient and stable cadmium-free blue-light-emitting device, which has remained a challenge because of the inferior photophysical properties of blue-light-emitting materials2,3. Here we present the synthesis of ZnSe-based blue-light-emitting quantum dots with a quantum yield of unity. We found that hydrofluoric acid and zinc chloride additives are effective at enhancing luminescence efficiency by eliminating stacking faults in the ZnSe crystalline structure. In addition, chloride passivation through liquid or solid ligand exchange leads to slow radiative recombination, high thermal stability and efficient charge-transport properties. We constructed double quantum dot emitting layers with gradient chloride content in a light-emitting diode to facilitate hole transport, and the resulting device showed an efficiency at the theoretical limit, high brightness and long operational lifetime. We anticipate that our efficient and stable blue quantum dot light-emitting devices can facilitate the development of electroluminescent full-colour displays using quantum dots.

Tumor-infiltrating lymphocyte therapy: Clinical aspects and future developments in this breakthrough cancer treatment.

Tumor-infiltrating lymphocyte (TIL) therapy is a promising approach for treating refractory or advanced solid cancers by using autologous TILs harvested from cancer tissues. Despite the heterogeneity of cancer, TIL therapy can potentially produce a positive therapeutic response, including complete remission. After decades of research on lymphocyte functions, culture/expansion methods, therapeutic protocols, and multiple clinical trials, TIL therapy has finally reached a stage where it can be formally approved for clinical use. TIL therapy is expected to hold a unique position among anti-cancer therapeutic options as a standard intervention. To successfully introduce TIL therapy into clinical settings, there is a need to expand therapeutic indications and set up the best protocols for cancer tissue sampling and manufacturing, and related clinical trials. Moreover, studies on next-generation TIL therapy have already begun, and post-approval real-world data will promote and support further research.

Nickel Oxide Hole Injection Layers for Balanced Charge Injection in Quantum Dot Light-Emitting Diodes.

Quantum dot (QD) light-emitting diodes (QLEDs) are promising for next-generation displays, but suffer from carrier imbalance arising from lower hole injection compared to electron injection. A defect engineering strategy is reported to tackle transport limitations in nickel oxide-based inorganic hole-injection layers (HILs) and find that hole injection is able to enhance in high-performance InP QLEDs using the newly designed material. Through optoelectronic simulations, how the electronic properties of NiOx affect hole injection efficiency into an InP QD layer, finding that efficient hole injection depends on lowering the hole injection barrier and enhancing the acceptor density of NiOx is explored. Li doping and oxygen enriching are identified as effective strategies to control intrinsic and extrinsic defects in NiOx, thereby increasing acceptor density, as evidenced by density functional theory calculations and experimental validation. With fine-tuned inorganic HIL, InP QLEDs exhibit a luminance of 45 200 cd m-2 and an external quantum efficiency of 19.9%, surpassing previous inorganic HIL-based QLEDs. This study provides a path to designing inorganic materials for more efficient and sustainable lighting and display technologies.

Development of an Acute Pain Assessment Tool for Patients in Post-anesthesia Care Units.

BACKGROUND: Post-operative pain is a common form of acute pain. Objective pain assessment in post-anesthesia care units after surgery is useful regardless of the patient's condition. AIMS: This study aimed to develop and evaluate an acute pain assessment tool for patients in post-anesthesia care units. DESIGN: This was a cross-sectional observational study comprising two stages: scale development and psychometric evaluation. SETTINGS:  . PARTICIPANTS/SUBJECTS:  . METHODS: Scale items were developed based on a literature review and content validity by experts. The validity and interrater reliability of the pain scale were evaluated using data from 218 patients admitted to the post-anesthesia care unit at a university hospital. A receiver operating characteristic curve was used to identify the sensitivity and specificity for determining the cutoff point for acute pain. RESULTS: We developed an objective acute pain scale, called the APA5, which ranges from 0-10 and comprises behavioral (facial and verbal expressions and body movement) and physiological (changes in heart rate and blood pressure) responses. The APA5 is valid and reliable for assessing acute pain in the recovery room. Sensitivity and specificity were acceptable when the cutoff was 2 out of 10 points. CONCLUSIONS: The APA5 is an easy and simple tool for measuring pain in patients in post-anesthesia care units who have difficulties with self-reporting.

Bifunctional Electron-Transporting Agent for Red Colloidal Quantum Dot Light-Emitting Diodes.

Indium phosphide (InP) quantum dots have enabled light-emitting diodes (LEDs) that are heavy-metal-free, narrow in emission linewidth, and physically flexible. However, ZnO/ZnMgO, the electron-transporting layer (ETL) in high-performance red InP/ZnSe/ZnS LEDs, suffers from high defect densities, quenches luminescence when deposited on InP, and induces performance degradation that arises due to trap migration from the ETL to the InP emitting layer. We posited that the formation of Zn2+ traps on the outer ZnS shell, combined with sulfur and oxygen vacancy migration between ZnO/ZnMgO and InP, may account for this issue. We synthesized therefore a bifunctional ETL (CNT2T, 3',3'″,3'″″-(1,3,5-triazine-2,4,6-triyl)tris(([1,1'-biphenyl]-3-carbonitrile)) designed to passivate Zn2+ traps locally and in situ and to prevent vacancy migration between layers: the backbone of the small molecule ETL contains a triazine electron-withdrawing unit to ensure sufficient electron mobility (6 × 10-4 cm2 V-1 s-1), and the star-shaped structure with multiple cyano groups provides effective passivation of the ZnS surface. We report as a result red InP LEDs having an EQE of 15% and a luminance of over 12,000 cd m-2; this represents a record among organic-ETL-based red InP LEDs.

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Combined OX40 Agonist and PD-1 Inhibitor Immunotherapy Improves the Efficacy of Vascular Targeted Photodynamic Therapy in a Urothelial Tumor Model.

PURPOSE: Vascular targeted photodynamic therapy (VTP) is a nonsurgical tumor ablation approach used to treat early-stage prostate cancer and may also be effective for upper tract urothelial cancer (UTUC) based on preclinical data. Toward increasing response rates to VTP, we evaluated its efficacy in combination with concurrent PD-1 inhibitor/OX40 agonist immunotherapy in a urothelial tumor-bearing model. EXPERIMENTAL DESIGN: In mice allografted with MB-49 UTUC cells, we compared the effects of combined VTP with PD-1 inhibitor/OX40 agonist with those of the component treatments on tumor growth, survival, lung metastasis, and antitumor immune responses. RESULTS: The combination of VTP with both PD-1 inhibitor and OX40 agonist inhibited tumor growth and prolonged survival to a greater degree than VTP with either immunotherapeutic individually. These effects result from increased tumor infiltration and intratumoral proliferation of cytotoxic and helper T cells, depletion of Treg cells, and suppression of myeloid-derived suppressor cells. CONCLUSIONS: Our findings suggest that VTP synergizes with PD-1 blockade and OX40 agonist to promote strong antitumor immune responses, yielding therapeutic efficacy in an animal model of urothelial cancer.

Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies.

With improved understanding of cancer biology and technical advancements in non-invasive management of urological malignancies, there is renewed interest in photodynamic therapy (PDT) as a means of focal cancer treatment. The application of PDT has also broadened as a result of development of better-tolerated and more effective photosensitizers. Vascular-targeted PDT (VTP) using padeliporfin, which is a water-soluble chlorophyll derivative, allows for tumor-specific cytotoxicity and has demonstrated efficacy in the management of urologic malignancies. Herein, we describe the evolution of photodynamic therapy in urologic oncology and the role of VTP in emerging treatment paradigms.

Prognostic significance of Human epidermal growth factor receptor-2 expression in patients with resectable gastric adenocarcinoma.

BACKGROUND: The purpose of this study was to investigate the correlation between human epidermal growth factor receptor 2 (HER2) overexpression and clinicopathologic factors and overall survival rate in patients who underwent curative gastrectomy for gastric adenocarcinoma. METHODS: Among patients who underwent curative gastrectomy for gastric adenocarcinoma at Inje University Paik Hospital from January 2012 to December 2015, 782 patients underwent an immunohistochemical analysis to evaluate HER2 expression levels. Clinicopathologic records that were collected from a gastric cancer database were retrospectively reviewed to identify clinicopathologic factors and survival rates of the patients. RESULTS: HER2 overexpression was detected in 166 patients (21.2%). There was a statistically significant correlation between HER2 expression level and sex (p = 0.013), histologic differentiation (p < 0.001), Lauren classification (p < 0.001), and T pathologic stage (p = 0.022). There were no statistically significant relationships between HER2 expression level and overall 5-year survival rate (p = 0.775) and overall 5-year survival rate of gastric adenocarcinoma classified according to the TNM stage (stage I: p = 0.756, stage II: p = 0.571, stage III: p = 0.704). The HER2 expression level was not affected by the overall 5-year survival rate in the uni- and multivariate analyses. CONCLUSIONS: In this study, the HER2 overexpression rate in gastric adenocarcinoma was 21.2% and was observed in well- and moderately differentiated types according to histologic differentiation, intestinal type according to the Lauren classification, male, and low T stage. There was no correlation between HER2 expression level and overall 5-year survival rate, and HER2 expression level was not associated with independent prognostic factors.

Effectiveness of the combination of vascular targeted photodynamic therapy and anti-cytotoxic T-lymphocyte-associated antigen 4 in a preclinical mouse model of urothelial carcinoma.

OBJECTIVE: To investigate the effectiveness of combination treatment of vascular targeted photodynamic therapy and anti-cytotoxic T-lymphocyte-associated antigen 4 immunotherapy in a mouse model of urothelial carcinoma. METHODS: We used C57BL/6 mice injected with murine bladder 49 cell line. Mice were randomly allocated into four treatment groups: vascular targeted photodynamic therapy only, anti-cytotoxic T-lymphocyte-associated antigen 4 only, combination therapy and control. We carried out three separate experiments that used distinct cohorts of mice: tumor growth and development of lung metastases monitored with bioluminescent imaging (n = 91); survival evaluated with Kaplan-Meier curves (n = 111); and tumor cell population studied with flow cytometry (n = 20). In a fourth experiment, we re-challenged tumors in previously treated mice and compared tumor growth with that of naïve mice. RESULTS: Combination therapy provided significant benefits over the other three treatment groups: prolonged survival (P < 0.0001), lower tumor signal (P < 0.0001) and decreased lung signal uptake (P ≤ 0.002). We also observed that mice previously treated with vascular targeted photodynamic therapy only or combination therapy did not present tumor growth after re-challenged tumors. CONCLUSIONS: Combination of vascular targeted photodynamic therapy with anti-cytotoxic T-lymphocyte-associated antigen 4 is an effective therapy in a urothelial carcinoma syngeneic mouse model. The present results suggest this therapy as a potential treatment option for both bladder and upper tract tumors in future clinical trials.

A Vertically Integrated Junctionless Nanowire Transistor.

A vertically integrated junctionless field-effect transistor (VJ-FET), which is composed of vertically stacked multiple silicon nanowires (SiNWs) with a gate-all-around (GAA) structure, is demonstrated on a bulk silicon wafer for the first time. The proposed VJ-FET mitigates the issues of variability and fabrication complexity that are encountered in the vertically integrated multi-NW FET (VM-FET) based on an identical structure in which the VM-FET, as recently reported, harnesses a source and drain (S/D) junction for its operation and is thus based on the inversion mode. Variability is alleviated by bulk conduction in a junctionless FET (JL-FET), where current flows through the core of the SiNW, whereas it is not mitigated by surface conduction in an inversion mode FET (IM-FET), where current flows via the surface of the SiNW. The fabrication complexity is reduced by the inherent JL structure of the JL-FET because S/D formation is not required. In contrast, it is very difficult to dope the S/D when it is positioned at each floor of a tall SiNW with greater uniformity and with less damage to the crystalline structure of the SiNW in a VM-FET. Moreover, when the proposed VJ-FET is used as nonvolatile flash memory, the endurance and retention characteristics are improved due to the above-mentioned bulk conduction.

Atorvastatin and rosuvastatin improve physiological parameters and alleviate immune dysfunction in metabolic disorders.

This study was designed to characterize the potential therapeutic effects of two statin drugs commonly used to treat dyslipidemia in inflammation-linked metabolic disorders related to type 2 diabetes. Atorvastatin (10 mg/kg/day) and rosuvastatin (3 mg/kg/day) were administered to mice with diet-induced obesity (DIO). The statins lowered serum total and LDL cholesterol levels, and improved the atherogenic index and cardiac risk index. Furthermore, the drugs decreased fasting glucose levels, improved glucose tolerance, and decreased fat tissue weight and adipocyte size; this was accompanied by an overall body weight loss tendency. The statins also improved antigen-specific immunity. The killing activity of cytotoxic T cells and exacerbation of IgG secretion levels were considerably normalized. Most importantly, serum tumor necrosis factor-α and interleukin 6 levels decreased, while their RNA expression levels in fat tissue were regulated by the statins as well. This study is the first to indicate that low doses of atorvastatin and rosuvastatin, the dosing regimen for which has been controversial, could significantly improve diabetes-related metabolic disorders, and could modulate pro-inflammatory cytokines, alleviating inflammation and simultaneously restoring overall humoral and cell-mediated immunity.

Treatment Effects of WST11 Vascular Targeted Photodynamic Therapy for Urothelial Cell Carcinoma in Swine.

PURPOSE: Surgical management of upper tract urothelial carcinoma requires kidney and ureter removal, compromising renal function. Nonsurgical alternatives have potentially prohibitive safety concerns. We examined the feasibility and safety of ablation of the ureter and renal pelvis using endoluminal vascular targeted photodynamic therapy in a porcine model. We also report the efficacy of WST11 vascular targeted photodynamic therapy in a murine model. MATERIALS AND METHODS: After receiving approval we performed a total of 28 endoluminal ablations in the ureters and renal pelvis of 18 swine. Intravenous infusion of WST11 (4 mg/kg) followed by 10-minute laser illumination was done via percutaneous access or a retrograde ureteroscopic approach. Animals were followed clinically with laboratory testing, imaging and histology, which were evaluated at several postablation time points. A murine xenograft was created with the 5637 human urothelial cell carcinoma line to determine sensitivity to this therapy. RESULTS: At 24 hours 50 mW/cm laser fluence produced superficial necrosis of the ureter. Deeper necrosis penetrating the muscularis propria or adventitia was produced by treatment with 200 mW/cm in the ureter and the renal pelvis. At 4 weeks superficial urothelium had regenerated over the treatment site. No symptomatic obstruction, clinically relevant hydronephrosis or abnormality of laboratory testing was noted up to 4 weeks. Of the mice 80% had no evidence of tumor 19 days after WST11 vascular targeted photodynamic therapy. CONCLUSIONS: Urothelial cell carcinoma appears to be sensitive to WST11 vascular targeted photodynamic therapy. The depth of WST11 vascular targeted photodynamic therapy treatment effects can be modulated in a dose dependent manner by titrating light intensity. Moreover, when applied to the porcine upper urinary tract, this treatment modality is feasible via antegrade and retrograde access.

NKG2D ligation relieves 2B4-mediated NK-cell self-tolerance in mice.

Along with MHC class I (MHCI), 2B4 provides nonredundant NK-cell inhibition in mice. The immunoregulatory role of 2B4 has been increasingly appreciated in models of tumor and viral infection, however, the interactions among 2B4, MHCI, and other activating NK-cell receptors remain uncertain. Here, we dissect the influence of two distinct inhibitory pathways in modulating NK-cell-mediated control of tumors expressing strong activating ligands, including RAE-1γ. In vitro cytotoxicity and in vivo peritoneal clearance assays using MHCI(+) CD48(+) (RMA-neo), MHCI(+) CD48(+) RAE-1γ (RMA-RAE-1γ), MHCI(-) CD48(+) (RMA-S-neo), and MHCI(-) CD48(+) RAE-1γ (RMA-S-RAE-1γ) tumor lines demonstrated that NKG2D activation supersedes the inhibitory effect of both 2B4- and MHCI-mediated immune-tolerance systems. Furthermore, 2B4KO mice subcutaneously challenged with RMA-neo and RMA-S-neo exhibited reduced tumor growth and significantly prolonged survival compared with WT mice, implying that 2B4 is constitutively engaged in the NK-cell tolerance mechanism in vivo. Nevertheless, the inhibitory effect of 2B4 is significantly attenuated when NK cells encountered highly stressed tumor cells expressing RAE-1γ, resulting in an immune response shift toward NK-cell activation and tumor regression. Therefore, our data highlight the importance of the 2B4-mediated inhibitory system as an alternate self-tolerance mechanism, whose role can be modulated by the strength of activating receptor signaling within the tumor microenvironment.

CCR10-mediated Enhancement of T Cell Trafficking for Improved Tumor Immunotherapy.

BACKGROUND/AIM: The effectiveness of adoptive T cell therapy for solid tumors remains suboptimal, partly attributed to insufficient T cell infiltration into the tumor site. A promising strategy involves directing T cells towards the tumor utilizing tumor-specific chemokine receptors. MATERIALS AND METHODS: We analyzed chemokine receptor expression in activated T cells and chemokine expression in breast and lung cancer using The Cancer Genome Atlas (TCGA) data. Subsequently, we generated 1G4 T cell receptor-engineered T (TCR-T) cells with CCR10 and performed in vitro and in vivo efficacy tests. RESULTS: CCR10 exhibited insufficient expression in various human T cells. Analysis of TCGA RNA sequencing data revealed elevated expression of the chemokine CCL28, the corresponding chemokine for CCR10, in breast and lung cancer. Consequently, we generated CCR10-1G4 TCR-T cells. CCR10-1G4 dual expressing TCR-T cells exhibited comparable cellular cytotoxicity but increased mobility compared to 1G4 TCR-T cells in vitro. Furthermore, injecting CCR10-1G4 dual expressing TCR-T cells into a xenograft tumor model demonstrated enhanced in vivo trafficking and a greater reduction of tumor burden. CONCLUSION: This study highlights the potential of CCR10 for developing efficient adoptive T-cell treatments targeting solid tumors.

Comparative study of immune response to local tumor destruction modalities in a murine breast cancer model.

Introduction: Immunotherapy is revolutionizing the management of multiple cancer types. However, only a subset of patients responds to immunotherapy. One mechanism of resistance is the absence of immune infiltrates within the tumor. In situ vaccine with local means of tumor destruction that can induce immunogenic cell death have been shown to enhance tumor T cell infiltration and increase efficacy of immune checkpoint blockade. Methods: Here, we compare three different forms of localize tumor destruction therapies: radiation therapy (RT), vascular targeted photodynamic therapy (VTP) and cryoablation (Cryo), which are known to induce immunogenic cell death, with their ability to induce local and systemic immune responses in a mouse 4T1 breast cancer model. The effects of combining RT, VTP, Cryo with anti-PD1 was also assessed. Results: We observed that RT, VTP and Cryo significantly delayed tumor growth and extended overall survival. In addition, they also induced regression of non-treated distant tumors in a bilateral model suggesting a systemic immune response. Flow cytometry showed that VTP and Cryo are associated with a reduction in CD11b+ myeloid cells (granulocytes, monocytes, and macrophages) in tumor and periphery. An increase in CD8+ T cell infiltration into tumors was observed only in the RT group. VTP and Cryo were associated with an increase in CD4+ and CD8+ cells in the periphery. Conclusion: These data suggest that cell death induced by VTP and Cryo elicit similar immune responses that differ from local RT.

Synaptopodin orchestrates actin organization and cell motility via regulation of RhoA signalling.

The Rho family of small GTPases (RhoA, Rac1 and Cdc42) controls signal-transduction pathways that influence many aspects of cell behaviour, including cytoskeletal dynamics. At the leading edge, Rac1 and Cdc42 promote cell motility through the formation of lamellipodia and filopodia, respectively. On the contrary, RhoA promotes the formation of contractile actin-myosin-containing stress fibres in the cell body and at the rear. Here, we identify synaptopodin, an actin-associated protein, as a novel regulator of RhoA signalling and cell migration in kidney podocytes. We show that synaptopodin induces stress fibres by competitive blocking of Smurf1-mediated ubiquitination of RhoA, thereby preventing the targeting of RhoA for proteasomal degradation. Gene silencing of synaptopodin in kidney podocytes causes the loss of stress fibres and the formation of aberrant non-polarized filopodia and impairment of cell migration. Together, these data show that synaptopodin is essential for the integrity of the podocyte actin cytoskeleton and for the regulation of podocyte cell migration.

Constitutively active androgen receptor splice variants expressed in castration-resistant prostate cancer require full-length androgen receptor.

Androgen receptor (AR) splice variants lacking the ligand binding domain (ARVs), originally isolated from prostate cancer cell lines derived from a single patient, are detected in normal and malignant human prostate tissue, with the highest levels observed in late stage, castration-resistant prostate cancer. The most studied variant (called AR-V7 or AR3) activates AR reporter genes in the absence of ligand and therefore, could play a role in castration resistance. To explore the range of potential ARVs, we screened additional human and murine prostate cancer models using conventional and next generation sequencing technologies and detected several structurally diverse AR isoforms. Some, like AR-V7/AR3, display gain of function, whereas others have dominant interfering activity. We also find that ARV expression increases acutely in response to androgen withdrawal, is suppressed by testosterone, and in some models, is coupled to full-length AR (AR-FL) mRNA production. As expected, constitutively active, ligand-independent ARVs such as AR-V7/AR3 are sufficient to confer anchorage-independent (in vitro) and castration-resistant (in vivo) growth. Surprisingly, this growth is blocked by ligand binding domain-targeted antiandrogens, such as MDV3100, or by selective siRNA silencing of AR-FL, indicating that the growth-promoting effects of ARVs are mediated through AR-FL. These data indicate that the increase in ARV expression in castrate-resistant prostate cancer is an acute response to castration rather than clonal expansion of castration or antiandrogen-resistant cells expressing gain of function ARVs, and furthermore, they provide a strategy to overcome ARV function in the clinic.

Single step isolation and activation of primary CD3+ T lymphocytes using alcohol-dispersed electrospun magnetic nanofibers.

Electrospun polymer nanofibers with entrapped magnetic nanoparticles (magnetic NP-NF) represent a novel scaffold substrate that can be functionalized for single-step isolation and activation of specific lymphocyte subsets. Using a surface-embedded T cell receptor ligand/trigger (anti-CD3 monoclonal antibody), we demonstrate, as proof of principle, the use of magnetic NP-NF to specifically isolate, enrich, and activate CD3(+) T cells from a heterogeneous cell mixture, leading to preferential expansion of CD8(+)CD3(+) T cells. The large surface area, adjustable antibody density, and embedded paramagnetic properties of the NP-NF permitted enhanced activation and expansion; its use represents a strategy that is amenable to an efficient selection process for adoptive cellular therapy as well as for the isolation of other cellular subsets for downstream translational applications.