Bispecific antibodies (bsAb) that target two independent epitopes or antigens have been extensively explored in translational and clinical studies since they were first developed in the 1960s. Many bsAbs are being tested in clinical trials for treating a variety of diseases, mostly cancer. Here, we provide an overview of various types of bsAbs in clinical studies and discuss their targets, safety profiles, and efficacy. We also highlight the current challenges, potential solutions, and future directions of bsAb development for cancer treatment.

Single-cell sequencing opens a new era for the investigation of tumor immune microenvironments (TIME). However, at single-cell resolution, a pan-cancer analysis that addresses the identity and diversity of TIMEs is lacking. Here, we first built a pan-cancer single-cell reference of TIMEs with refined subcell types and recognized new cell type–specific transcription factors. We then presented a pan-cancer view of the common features of the TIME and compared the variation of each immune cell type across patients and tumor types in the aspects of abundance, cell states, and cell communications. We found that the abundance and the cell states of dysfunctional T cells were most variable, whereas those of regulatory T cells were relatively stable. A subset of tumor-associated macrophages (TAM), PLTP+C1QC+ TAMs, may regulate the abundance of dysfunctional T cells through cytokine/chemokine signaling. The ligand–receptor communication network of TIMEs was tumor-type specific and dominated by the tumor-enriched immune cells. We additionally developed the single-cell TIME (scTIME) portal (http://scTIME.sklehabc.com) with the scTIME-specific analysis modules and a unified cell annotation. In addition to the immune cell compositions and correlation analysis using refined cell type classifications, the portal also provides cell–cell interaction and cell type–specific gene signature analysis. Our single-cell pan-cancer analysis and scTIME portal will provide more insights into the features of TIMEs, as well as the molecular and cellular mechanisms underlying immunotherapies.

Hematopoietic stem cell transplantation is an effective regenerative therapy for many malignant, inherited, or autoimmune diseases. However, our understanding of reconstituted hematopoiesis in transplant patients remains limited. Here, we uncover the reconstitution dynamics of human allogeneic hematopoietic stem and progenitor cells (HSPCs) at single-cell resolution after transplantation. Transplanted HSPCs underwent rapid and measurable changes during the first 30 days after transplantation, characterized by a strong proliferative response on the first day. Transcriptomic analysis of HSPCs enabled us to observe that immunoregulatory neutrophil progenitors expressing high levels of the S100A gene family were enriched in granulocyte colony-stimulating factor–mobilized peripheral blood stem cells. Transplant recipients who developed acute graft-versus-host disease (aGVHD) infused fewer S100A high immunoregulatory neutrophil progenitors, immunophenotyped as Lin - CD34 + CD66b + CD177 + , than those who did not develop aGVHD. Therefore, our study provides insights into the regenerative process of transplanted HSPCs in human patients and identifies a potential criterion for identifying patients at high risk for developing aGVHD early after transplant.