Adenovirus-Mediated Inducible Expression of a PD-L1 Blocking Antibody in Combination with Macrophage Depletion Improves Survival in a Mouse Model of Peritoneal Carcinomatosis

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local or regional expression of monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In this work, we describe a high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped with a mifepristone-inducible system for the controlled expression of an anti-programmed death ligand 1 (PD-L1) blocking antibody. The vector was tested in an immune-competent mouse model of colorectal cancer based on implantation of MC38 cells. A single local administration of HCA-EFZP-aPDL1 in subcutaneous lesions led to a significant reduction in tumor growth with minimal release of the antibody in the circulation. When the vector was tested in a more stringent setting (rapidly progressing peritoneal carcinomatosis), the antitumor effect was marginal even in combination with other immune-stimulatory agents such as polyinosinic-polycytidylic acid (pI:C), blocking mAbs for T cell immunoglobulin, mucin-domain containing-3 (TIM-3) or agonistic mAbs for 4-1BB (CD137). In contrast, macrophage depletion by clodronate liposomes enhanced the efficacy of HCA-EFZP-aPDL1. These results highlight the importance of addressing macrophage-associated immunoregulatory mechanisms to overcome resistance to ICIs in the context of colorectal cancer.     

MS900轧机液压锁的故障及分析

针对MS900轧机生产中遇到的问题,重点对因双锁取代单锁、液压锁安装位置错误及配套使用的换向阀型号不符等引发的故障及产生原因进行了分析。     

基于Visual Basic 开发机床主传动非常规变速系统的设计--重复转速的传动系统(实例之二)

本文介绍利用Visual Basic工具开发金属切削机床主传动非常规变速系统的设计总体结构，功能和方法，以重复转速的传动系统为例，重点介绍转速图的拟定过程，本系统具有界面美观，操作方便，易于理解的特点。     

多关节机器人通用体系结构的研究

结合一个五自由度教学工业两用型机器人应用实例，构造出多关节机器人通用体系结构，包括总体原型、机械结构、关节传动链、伺服驱动元件、电气控制系统、关节坐标系及其运动学方程、通信协议和软件设计思路等。通过实际使用表明，本文提出的通用体系结构是实用的、合理的。     

Kynar—500涂装工艺与涂层性能研究

介绍了Kynar－500涂料的涂装工艺，并对涂层的性能作了试验与分析。     

PET熔体输送系统中熔体温度自动控制方案

在热媒温度控制系统中以熔体温度作为主参数,组成串极调节系统。投入运行后,熔体温度稳定,调节阀动作平稳,效果良好。     

新桥硫铁矿二步骤回采工艺及充填方案的探讨

介绍了新桥硫铁矿二步骤回采工艺，并从技术经济角度对该矿所采用的充填料及充填系统进行了探讨。     

大型空分制氧站DCS调试技术

以宝钢集团浦钢60000 Nm3/h的大型空分制氧站DCS调试为基础,结合以往大型空分制氧站DCS调试经验,探讨了大型空分制氧站DCS调试的特点、施工组织、调试工艺及方法,并对控制回路试验、离心式压缩机防喘振控制组态、压缩机起停及控制逻辑、紧急停车及重要安全回路调试、组态临时变更管理等重点、难点及关键环节的调试技术进行了详细的总结、说明,旨在为其他同类工程提供参考与借鉴.