Electrophilic proximity-inducing synthetic adapters enhance universal T cell function by covalently enforcing immune receptor signaling.

Proximity-induction of cell-cell interactions via small molecules represents an emerging field in basic and translational sciences. Covalent anchoring of these small molecules represents a useful chemical strategy to enforce proximity; however, it remains largely unexplored for driving cell-cell interactions. In immunotherapeutic applications, bifunctional small molecules are attractive tools for inducing proximity between immune effector cells like T cells and tumor cells to induce tumoricidal function.

Mitogenomics of the Koryaks and Evens of the northern coast of the Sea of Okhotsk.

Due to the geographical proximity of the northern coast of the Sea of Okhotsk and Kamchatka Peninsula to the Beringia, the indigenous populations of these territories are of great interest for elucidating the human settlement history of northern Asia and America. Meanwhile, there is a clear shortage of genetic studies of the indigenous populations of the northern coast of the Sea of Okhotsk. Here, in order to examine their fine-scale matrilineal genetic structure, ancestry and relationships with neighboring populations, we analyzed 203 complete mitogenomes (174 of which are new) from population samples of the Koryaks and Evens of the northern coast of the Sea of Okhotsk and the Chukchi of the extreme northeast Asia.

Mitogenomics of modern Mongolic-speaking populations.

Here, we present a comprehensive data set of 489 complete mitogenomes (211 of which are new) from four Mongolic-speaking populations (Mongols, Barghuts, Khamnigans, and Buryats) to investigate their matrilineal genetic structure, ancestry and relationship with other ethnic groups. We show that along with very high levels of genetic diversity and lack of genetic differentiation, Mongolic-speaking populations exhibit strong genetic resemblance to East Asian populations of Chinese, Japanese, and Uyghurs. Phylogeographic analysis of complete mitogenomes reveals the presence of different components in the gene pools of modern Mongolic-speaking populations-the main East Eurasian component is represented by mtDNA lineages of East Asian, Siberian and autochthonous (the Baikal region/Mongolian) ancestry, whereas the less pronounced West Eurasian component can be ascribed to Europe and West Asia/Caucasus.

Development of a B-cell maturation antigen-specific T-cell antigen coupler receptor for multiple myeloma.

Background Aims: T cells engineered with synthetic receptors have delivered powerful therapeutic results for patients with relapsed/refractory hematologic malignancies. The authors have recently described the T-cell antigen coupler (TAC) receptor, which co-opts the endogenous T-cell receptor (TCR) and activates engineered T cells in an HLA-independent manner. Here the authors describe the evolution of a next-generation TAC receptor with a focus on developing a TAC-engineered T cell for multiple myeloma.

A Cross-Reactive Small Protein Binding Domain Provides a Model to Study Off-Tumor CAR-T Cell Toxicity.

Tumor-targeted chimeric antigen receptor (CAR)-engineered T lymphocytes (CAR-T cells) have demonstrated striking clinical success, but their use has been associated with a constellation of toxicities. A better understanding of the pathogenesis of these toxicities is required to improve the safety profile of CAR-T cells. Herein, we describe a xenograft model of off-tumor CAR-T cell-associated toxicity.