Discovery of Novel TLR7 Agonists as Systemic Agent for Combination With aPD1 for Use in Immuno-oncology.

We have designed and developed novel and selective TLR7 agonists that exhibited potent receptor activity in a cell-based reporter assay. , these agonists significantly induced secretion of cytokines IL-6, IL-1β, IL-10, TNFa, IFNa, and IP-10 in human and mouse whole blood. Pharmacokinetic and pharmacodynamic studies in mice showed a significant secretion of IFNα and TNFα cytokines.

Sintering Temperature Effect of Near-Zero Thermal Expansion MnZnSnN/Ti Composites.

Metal matrix composites with near-zero thermal expansion (NZTE) have gained significant popularity in high-precision industries due to their excellent thermal stability and mechanical properties. The incorporation of MnZnSnN, which possesses outstanding negative thermal expansion properties, effectively suppressed the thermal expansion of titanium. Highly dense MnZnSnN/Ti composites were obtained by adjusting the fabrication temperature.

Configuration Design and Dynamic Characteristics Analysis of Spacecraft Membrane Sunshield.

To meet the needs of large space telescopes, such as light weight, high folding ratio, and low manufacturing cost, a flexible deployable regular hexagonal membrane sunshield is proposed in this paper. Firstly, the dynamic equation of the membrane plane is established by the micro-element method. Then, the response surface method is used to obtain the mathematical model of the fundamental frequency of the membrane sunshield.

Stress Superposition Method and Mechanical Properties Analysis of Regular Polygon Membranes.

In this paper, the stress superposition method (SSM) is proposed to solve the stress distribution of regular polygon membranes. The stress-solving coefficient and the calculation formula of arbitrary point stress of regular polygon membrane are derived. The accuracy of the SSM for calculating stresses in regular polygonal membranes is verified by comparing the calculation results of the SSM with the finite element simulation results.

Synthesis and Biological Evaluation of a Carbamate-Containing Tubulysin Antibody-Drug Conjugate.

Antibody-drug conjugates (ADCs) use antibodies to deliver cytotoxic payloads directly into tumor cells via specifically binding to the target cell surface antigens. ADCs can enhance the anti-tumor effects of antibodies, and increase the delivery of cytotoxic payloads to cancer cells with a better therapeutic index. An ADC was prepared with a potent carbamate-containing tubulysin analogue attached to an anti-mesothelin antibody via a Cit-Val dipeptide linker.

High-Throughput Platform to Identify Antibody Conjugation Sites from Antibody-Drug Conjugate Libraries.

Antibody-drug conjugates (ADCs) are a therapeutic modality that traditionally enable the targeted delivery of highly potent cytotoxic agents to specific cells such as tumor cells. More recently, antibodies have been used to deliver molecules such as antibiotics, antigens, and adjuvants to bacteria or specific immune cell subsets. Site-directed mutagenesis of proteins permits more precise control over the site and stoichiometry of their conjugation, giving rise to homogeneous chemically defined ADCs.

Universal Affinity Capture Liquid Chromatography-Mass Spectrometry Assay for Evaluation of Biotransformation of Site-Specific Antibody Drug Conjugates in Preclinical Studies.

Antibody drug conjugates (ADCs) can undergo in vivo biotransformation (e.g., payload metabolism, deconjugation) leading to reduced or complete loss of activity.

Adnectin-drug conjugates for Glypican-3-specific delivery of a cytotoxic payload to tumors.

Tumor-specific delivery of cytotoxic agents remains a challenge in cancer therapy. Antibody-drug conjugates (ADC) deliver their payloads to tumor cells that overexpress specific tumor-associated antigens-but the multi-day half-life of ADC leads to high exposure even of normal, antigen-free, tissues and thus contributes to dose-limiting toxicity. Here, we present Adnectin-drug conjugates, an alternative platform for tumor-specific delivery of cytotoxic payloads.

Structure-activity relationship studies of illudins: analogues possessing a spiro-cyclobutane ring.

Bicyclic and tricyclic analogues of anticancer sesquiterpene illudin S have been synthesized. These contain a spiro-cyclobutane instead of spiro-cyclopropane structure. The cytotoxicity of the former is less than that of the corresponding cyclopropane-containing compounds.