Engineering CD3/CD137 Dual Specificity into a DLL3-Targeted T-Cell Engager Enhances T-Cell Infiltration and Efficacy against Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) is an aggressive cancer for which immune checkpoint inhibitors (ICI) have had only limited success. Bispecific T-cell engagers are promising therapeutic alternatives for ICI-resistant tumors, but not all patients with SCLC are responsive. Herein, to integrate CD137 costimulatory function into a T-cell engager format and thereby augment therapeutic efficacy, we generated a CD3/CD137 dual-specific Fab and engineered a DLL3-targeted trispecific antibody (DLL3 trispecific).

Exploitation of Elevated Extracellular ATP to Specifically Direct Antibody to Tumor Microenvironment.

The extracellular adenosine triphosphate (ATP) concentration is highly elevated in the tumor microenvironment (TME) and remains tightly regulated in normal tissues. Using phage display technology, we establish a method to identify an antibody that can bind to an antigen only in the presence of ATP. Crystallography analysis reveals that ATP bound in between the antibody-antigen interface serves as a switch for antigen binding.

Protonation-induced self-assembly of bis-phenanthroline macrocycles into nanofibers arrayed with tetrachloroaurate, hexachloroplatinate or phosphomolybdate ions.

One-dimensional self-assembly of macrocycles is one of the important strategies for constructing fibrous nanomaterials with anisotropic functions such as one-dimensional transport and accumulation of molecules and ions. Herein we report on the synthesis and properties of self-assembled nanofibers using macrocycles to develop a multipurpose template for one-dimensional array of noble metal ions. The nanofibers were prepared by protonation-induced self-assembly of bis-phenanthroline macrocycles, which have enabled the accumulation of some metal-containing anions, such as tetrachloroaurate, hexachloroplatinate and phosphomolybdate.

Selection of mRNA 5'-untranslated region sequence with high translation efficiency through ribosome display.

The 5'-untranslated region (5'-UTR) of mRNAs functions as a translation enhancer, promoting translation efficiency. Many in vitro translation systems exhibit a reduced efficiency in protein translation due to decreased translation initiation. The use of a 5'-UTR sequence with high translation efficiency greatly enhances protein production in these systems.