In vivo neutrophils hitchhiking for tumor targeting and microenvironment regulation boosts oncolytic virus therapy.

Neutrophils constitute a substantial proportion of the immune cell population infiltrating tumors, where they play a pivotal role in establishing an immunosuppressive microenvironment to facilitate tumor growth. Our clinical investigation has unveiled that, following oncolytic virus (OV) treatment, immunosuppressive neutrophils could lead to T cell exhaustion and compromised antitumor efficacy. In this study, we devise a dual-functional conjugation strategy that enables OVs to selectively bind with circulating neutrophils and initiate their death.

A First-in-Human Study of Givastomig, a CLDN18.2 and 4-1BB Bispecific Antibody, as Monotherapy in Patients with CLDN18.2-Positive Advanced or Metastatic Solid Tumors.

Purpose: Givastomig is a bispecific antibody that targets CLDN18.2 and conditionally activates local 4-1BB-expressing T cells. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of givastomig in advanced solid tumors.

Tailoring an intravenously injectable oncolytic virus for augmenting radiotherapy.

Oncolytic viruses (OVs) combined with radiotherapy (RT) show promise but are limited by challenges such as poor intravenous delivery and insufficient RT-induced DNA damage. In this study, an oncolytic adenovirus (AD) formulation, RadioOnco (AD@PSSP), is developed to improve delivery, infectivity, immune response, and RT efficacy. The multifunctional polyethylenimine (PEI)-selenium-polyethylene glycol (PEG) (PSSP) enhances intravenous delivery, shields the virus from rapid clearance, and enables targeted delivery to tumor sites after RT.

Soft-matter-induced orderings in a solid-state van der Waals heterostructure.

Deoxyribose nucleic acid (DNA), a type of soft matter, is often considered a promising building block to fabricate and investigate hybrid heterostructures with exotic functionalities. However, at this stage, investigations on DNA-enabled nanoelectronics have been largely limited to zero-dimensional (0D) and/or one-dimensional (1D) structures. Exploring their potential in higher dimensions, particularly in combination with hard matter solids such as van der Waals (vdW) two-dimensional (2D) materials, has proven challenging.

Microneedle-based nanodrugs for tumor immunotherapy.

Microneedles have emerged as a promising and effective method for delivering therapeutic drugs and immunobiologics to treat various diseases. It is widely recognized that immune therapy has limited efficacy in solid tumors due to physical barriers and the immunosuppressive tumor microenvironment. Microneedle-based nanodrugs (NDMNs) offer a novel approach to overcome these limitations.

Coacervate vesicles assembled by liquid-liquid phase separation improve delivery of biopharmaceuticals.

Vesicles play critical roles in cellular materials storage and signal transportation, even in the formation of organelles and cells. Natural vesicles are composed of a lipid layer that forms a membrane for the enclosure of substances inside. Here we report a coacervate vesicle formed by the liquid-liquid phase separation of cholesterol-modified DNA and histones.

Claudin 18.2-targeting antibody-drug conjugate CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer (KYM901): a multicentre, open-label, single-arm, phase 1 trial.

Background: CMG901 is a novel first-in-class antibody-drug conjugate with a humanised anticlaudin 18.2 antibody linked to microtubule-disrupting agent monomethyl auristatin E. We aimed to assess the antitumour activity and safety of CMG901 in patients with advanced gastric or gastro-oesophageal junction cancer and other solid tumours.

Non-secreting IL12 expressing oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade glioma: a phase I trial.

Malignant glioma is a highly fatal central nervous system malignancy with high recurrence rates. Oncolytic viruses offer potential treatment but need improvement in efficacy and safety. Here we describe a phase I, dose-escalating, single arm trial (ChiCTR2000032402) to study the safety of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in patients with recurrent high-grade glioma that connects with the ventricular system.

Urban growth simulation and scenario projection for the arid regions using heuristic cellular automata.

Arid regions tend to form compact urban patterns that have significant implications on urban growth and future urban patterns. Spatial simulation and projection using cellular automata (CA)-based models are important for achieving sustainable urban development in arid regions. In response to this need, we developed a new CA model (GSA-CA) using the gravitational search algorithm (GSA) to capture and project urban growth patterns in arid regions.

Recent developments in two-dimensional molybdenum disulfide-based multimodal cancer theranostics.

Recent advancements in cancer research have led to the generation of innovative nanomaterials for improved diagnostic and therapeutic strategies. Despite the proven potential of two-dimensional (2D) molybdenum disulfide (MoS) as a versatile platform in biomedical applications, few review articles have focused on MoS-based platforms for cancer theranostics. This review aims to fill this gap by providing a comprehensive overview of the latest developments in 2D MoS cancer theranostics and emerging strategies in this field.

COVID-19 and the risk of acute cardiovascular diseases: a two-sample Mendelian randomization study.

Background: Evidence suggests that coronavirus disease 2019 (COVID-19) is associated with the risk of cardiovascular diseases (CVDs). However, the results are inconsistent, and the causality remains to be established. We aimed to investigate the potential causal relationship between COVID-19 and CVDs by using two-sample Mendelian randomization (MR) analysis.

Erratum: A Novel Pak1/ATF2/miR-132 Signaling Axis Is Involved in the Hematogenous Metastasis of Gastric Cancer Cells.

[This corrects the article DOI: 10.1016/j.omtn.

Progress in oncolytic viruses modified with nanomaterials for intravenous application.

In oncolytic virus (OV) therapy, a critical component of tumor immunotherapy, viruses selectively infect, replicate within, and eventually destroy tumor cells. Simultaneously, this therapy activates immune responses and mobilizes immune cells, thereby eliminating residual or distant cancer cells. However, because of OVs' high immunogenicity and immune clearance during circulation, their clinical applications are currently limited to intratumoral injections, and their use is severely restricted.

Erythrocyte-Leveraged Oncolytic Virotherapy (ELeOVt): Oncolytic Virus Assembly on Erythrocyte Surface to Combat Pulmonary Metastasis and Alleviate Side Effects.

Despite being a new promising tool for cancer therapy, intravenous delivery of oncolytic viruses (OVs) is greatly limited by poor tumor targeting, rapid clearance in the blood, severe organ toxicity, and cytokine release syndrome. Herein, a simple and efficient strategy of erythrocyte-leveraged oncolytic virotherapy (ELeOVt) is reported, which for the first time assembled OVs on the surface of erythrocytes with up to near 100% efficiency and allowed targeted delivery of OVs to the lung after intravenous injection to achieve excellent treatment of pulmonary metastases while greatly improving the biocompatibility of OVs as a drug. Polyethyleneimine (PEI) as a bridge to assemble OVs on erythrocytes also played an important role in promoting the transfection of OVs.

Virus-Protein Corona Replacement Strategy to Improve the Antitumor Efficacy of Intravenously Injected Oncolytic Adenovirus.

Intravenous administration of oncolytic adenoviruses (OVs) is a hopeful tumor therapeutic modality. However, the sharp clearance of OVs by the immune system dampens its effectiveness. Many studies have attempted to extend the circulation of intravenously administered OVs, almost all by preventing OVs from binding to neutralizing antibodies and complements in the blood, but the results have not been satisfactory.

Engineered bacterial outer membrane vesicles encapsulating oncolytic adenoviruses enhance the efficacy of cancer virotherapy by augmenting tumor cell autophagy.

Oncolytic adenovirus (Ad) infection promotes intracellular autophagy in tumors. This could kill cancer cells and contribute to Ads-mediated anticancer immunity. However, the low intratumoral content of intravenously delivered Ads could be insufficient to efficiently activate tumor over-autophagy.

Self-assembled short peptides: Recent advances and strategies for potential pharmaceutical applications.

Self-assembled short peptides have intrigued scientists due to the convenience of synthesis, good biocompatibility, low toxicity, inherent biodegradability and fast response to change in the physiological environment. Therefore, it is necessary to present a comprehensive summary of the recent advances in the last decade regarding the construction, route of administration and application of self-assembled short peptides based on the knowledge on their unique and specific ability of self-assembly. Herein, we firstly explored the molecular mechanisms of self-assembly of short peptides, such as non-modified amino acids, as well as Fmoc-modified, N-functionalized, and C-functionalized peptides.

Adverse events of PD-(L)1 inhibitors plus anti-VEGF(R) agents compared with PD-(L)1 inhibitors alone for cancer patients: a systematic review and meta-analysis.

Anti-PD-(L)1 antibody monotherapy or in combination with VEGF(R) blockade has been applied widely for cancer treatment. Whether combination therapy increases irAEs still remains controversial. A systematic review and meta-analysis comparing PD-(L)1 and VEGF(R) blockade combination therapy with PD-(L)1 inhibitors alone was performed.

Inhibition of Tumor Metastasis by Liquid-Nitrogen-Shocked Tumor Cells with Oncolytic Viruses Infection.

Despite the superior tumor lytic efficacy of oncolytic viruses (OVs), their systemic delivery still faces the challenges of limited circulating periods, poor tumor tropism, and spontaneous antiviral immune responses. Herein, a virus-concealed tumor-targeting strategy enabling OVs' delivery toward lung metastasis via systemic administration is described. The OVs can actively infect, be internalized, and cloak into tumor cells.

Oncolytic Virus-Driven Biotherapies from Bench to Bedside.

With advances in cancer biology and an ever-deepening understanding of molecular virology, oncolytic virus (OV)-driven therapies have developed rapidly and become a promising alternative to traditional cancer therapies. In recent years, satisfactory results for oncolytic virus therapy (OVT) are achieved at both the cellular and organismal levels, and efforts are being increasingly directed toward clinical trials. Unfortunately, OVT remains ineffective in these trials, especially when performed using only a single OV reagent.