Preclinical and clinical trials of oncolytic vaccinia virus in cancer immunotherapy:a comprehensive review

Oncolytic virotherapy has emerged as a promising treatment for human cancers owing to an ability to elicit curative effects via systemic administration.Tumor cells often create an unfavorable immunosuppressive microenvironment that degrade viral structures and impede viral replication;however,recent studies have established that viruses altered via genetic modifications can serve as effective oncolytic agents to combat hostile tumor environments.Specifically,oncolytic vaccinia virus(OVV)has gained popularity owing to its safety,potential for systemic delivery,and large gene insertion capacity.This review highlights current research on the use of engineered mutated viruses and gene-armed OVVs to reverse the tumor microenvironment and enhance antitumor activity in vitro and in vivo,and provides an overview of ongoing clinical trials and combination therapies.In addition,we discuss the potential benefits and drawbacks of OVV as a cancer therapy,and explore different perspectives in this field.

Dynamic compliance of energy-saving legged elastic parallel joints for quadruped robots:design and realization

Achieving dynamic compliance for energy-efficient legged robot motion is a longstanding challenge.Although recent predictive control methods based on single-rigid-body models can generate dynamic motion,they all assume infinite energy,making them unsuitable for prolonged robot operation.Addressing this issue necessitates a mechanical structure with energy storage and a dynamic control strategy that incorporates feedback to ensure stability.This work draws inspiration from the efficiency of bio-inspired muscle–tendon networks and proposes a controllable torsion spring leg structure.The design integrates a spring-loaded inverted pendulum model and adopts feedback delays and yield springs to enhance the delay effects.A leg control model that incorporates motor loads is developed to validate the response and dynamic performance of a leg with elastic joints.This model provides torque to the knee joint,effectively reducing the robot’s energy consumption through active or passive control strategies.The benefits of the proposed approach in agile maneuvering of quadruped robot legs in a realistic scenario are demonstrated to validate the dynamic motion performance of the leg with elastic joints with the advantage of energy-efficient legs.

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

Body trajectory optimisation of walking gait for a quadruped robot

To ensure that the robot can follow the planned trajectory,smooth switching between swinging legs and a smooth transition of motion process is realised.The previous motion planning work is analysed,and a method for improving the optimisation objective function and constraint conditions is proposed to eliminate the sudden change of acceleration and reduce the peak value of acceleration change.This method eliminates the impact phenomenon in the motor drive process and reduces the motor drive energy consumption,thus ensuring the smooth and consistent movement of the robot.The results show that the improved optimisation method has a better motion effect than the previous approach in terms of centre of mass motion speed,trajectory fitting and body posture change,and realises more robust motion of quadruped robots in a senseless state.