The redirected killing of PD-L1 positive tumor cells by the expanded mucosa-associated invariant T (MAIT) cells is mediated with a bispecific antibody targeting TCR Vα7.2 and PD-L1.

Pan-T cell targeting by CD3-based T cell engagers has brought program-shift treatment and management of blood tumors. However, these modalities have been shown to provoke all types of T cells leading to cytokine storm syndrome, and activate Treg cells. Thus, modulating and potentiating the antitumor responses of a specific T cell subset was encouraged.

Anti-TGF-β/PD-L1 bispecific antibody promotes T cell infiltration and exhibits enhanced antitumor activity in triple-negative breast cancer.

Background: Agents blocking programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) have been approved for triple-negative breast cancer (TNBC). However, the response rate of anti-PD-1/PD-L1 is still unsatisfactory, partly due to immunosuppressive factors such as transforming growth factor-beta (TGF-β). In our previous pilot study, the bispecific antibody targeting TGF-β and murine PD-L1 (termed YM101) showed potent antitumor effect.

Combination of oral STING agonist MSA-2 and anti-TGF-β/PD-L1 bispecific antibody YM101: a novel immune cocktail therapy for non-inflamed tumors.

Background: Non-inflamed tumors, including immune-excluded and immune-desert tumors, are commonly resistant to anti-PD-1/PD-L1 (α-PD-1/PD-L1) therapy. Our previous study reported the potent antitumor activity of anti-TGF-β/PD-L1 bispecific antibody YM101 in immune-excluded tumors. However, YM101 had limited antitumor activity in immune-desert models.

Vγ2 x PD-L1, a Bispecific Antibody Targeting Both the Vγ2 TCR and PD-L1, Improves the Anti-Tumor Response of Vγ2Vδ2 T Cell.

The potent cytotoxic property of Vγ2Vδ2 T cells makes them attractive for adoptive T cell transfer therapy. The transfusing of the expanded Vγ2Vδ2 T cells into cancer patients shows well-tolerated, but the clinical response rates are required to be improved, implying that there is still an unmet efficacy with low toxicity for this novel anti-tumor therapy. In this study, we test the anti-tumor efficacy of a Y-body-based bispecific antibody (bsAb) Vγ2 x PD-L1 that preferentially redirects Vγ2Vδ2 T cells to combat PD-L1 positive tumor cells.

Subsequent malaria enhances virus-specific T cell immunity in SIV-infected Chinese rhesus macaques.

Background: Coinfection with HIV and Plasmodium parasites is fairly common, but the sequence of infection with these two pathogens and their impact on disease progression are poorly understood.

Methods: A Chinese rhesus macaque HIV and Plasmodium coinfection model was established to compare the impact of pre-existing and subsequent malaria on the progression of SIV infection.

Results: We found that a pre-existing malaria caused animals to produce a greater number of CD4CCR5 T cells for SIV replication, resulting in higher viral loads.

Effect of a Care Bundle Combined with Continuous Positive Airway Pressure in the Postanesthesia Care Unit on Rapid Recovery after Pulmonary Tumor Resection.

Objective: To study the effect of a care bundle combined with continuous positive airway pressure (CPAP) in the postanesthesia care unit (PACU) on rapid recovery after pulmonary tumor resection.

Methods: A total of 135 patients requiring anesthesia resuscitation after pulmonary tumor resection in our hospital from June 2020 to February 2021 were selected. They were randomly divided into three groups: the PACU experimental group, PACU control group, and operating room resuscitation (OR) group.

Combine and conquer: manganese synergizing anti-TGF-β/PD-L1 bispecific antibody YM101 to overcome immunotherapy resistance in non-inflamed cancers.

Background: Our previous work showed that the anti-TGF-β/PD-L1 bispecific antibody YM101 effectively overcame anti-PD-L1 resistance in immune-excluded tumor models. However, in immune-desert models, the efficacy of YM101 was limited. Bivalent manganese (Mn) is identified as a natural stimulator of interferon genes (STING) agonist, which might enhance cancer antigen presentation and improve the therapeutic effect of YM101.

RBD-homodimer, a COVID-19 subunit vaccine candidate, elicits immunogenicity and protection in rodents and nonhuman primates.

The pandemic of COVID-19 caused by SARS-CoV-2 has raised a new challenges to the scientific and industrious fields after over 1-year spread across different countries. The ultimate approach to end the pandemic is the timely application of vaccines to achieve herd immunity. Here, a novel SARS-CoV-2 receptor-binding domain (RBD) homodimer was developed as a SARS-CoV-2 vaccine candidate.

Bispecific Antibody PD-L1 x CD3 Boosts the Anti-Tumor Potency of the Expanded Vγ2Vδ2 T Cells.

Vγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111 prompted fresh CD8+ T cell-mediated lysis of H358 cells, but spared this effect on the fresh Vδ2+ T cells enriched from the same donors, which suggested that Y111 could bypass the anti-tumor capacity of the fresh Vγ2Vδ2 T cells.

The construction, expression, and enhanced anti-tumor activity of YM101: a bispecific antibody simultaneously targeting TGF-β and PD-L1.

Background: Therapeutic antibodies targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis induce potent and durable anti-tumor responses in multiple types of cancers. However, only a subset of patients benefits from anti-PD-1/PD-L1 therapies. As a negative regulator of anti-tumor immunity, TGF-β impairs the efficacy of anti-PD-1/PD-L1 and induces drug resistance.

CD38: targeted therapy in multiple myeloma and therapeutic potential for solid cancers.

Introduction: CD38 is expressed by some cells of hematological malignancies and tumor-related immunosuppressive cells, including regulatory T cells, regulatory B cells, and myeloid-derived suppressor cells. CD38 is an effective target in some hematological malignancies such as multiple myeloma (MM). Daratumumab (Dara), a CD38-targeting antibody, can eliminate CD38 immune suppressor cells and is regarded as a standard therapy for MM because of its outstanding clinical efficacy.

SIV infection aggravates malaria in a Chinese rhesus monkey coinfection model.

Background: The co-occurrence of human immunodeficiency virus (HIV) infection and malaria in humans in endemic areas raises the question of whether one of these infections affects the course of the other. Although epidemiological studies have shown the impact of HIV infection on malaria, the mechanism(s) are not yet fully understood. Using a Chinese rhesus macaque coinfection model with simian immunodeficiency virus (SIV) and Plasmodium cynomolgi (Pc) malaria, we investigated the effect of concurrent SIV infection on the course of malaria and the underlying immunological mechanism(s).

A novel asymmetrical anti-HER2/CD3 bispecific antibody exhibits potent cytotoxicity for HER2-positive tumor cells.

Background: Human epidermal growth factor receptor 2 (HER2) is overexpressed in multiple cancers, which is associated with poor prognosis. Herceptin and other agents targeting HER2 have potent antitumor efficacy in patients with HER2-positive cancers. However, the development of drug resistance adversely impacts the efficacy of these treatments.

[Clinical diagnosis and treatment of multiple level thoracolumbar spinal fractures].

Objective: To investigate the clinical characteristics and methods of diagnosis and treatment multiple level thoracolumbar spinal fractures.

Methods: From March 2002 to March 2006, 17 patients with 35 thoracolumbar spinal fractures were treated, 13 males and 4 females, aged 21-52 years old (36.4 on average), among whom there were 10 cases of traffic accident injury and 7 of high falling injury.

Raising allo-restricted cytotoxic T lymphocytes by co-culture of murine splenocytes with autologous macrophage bearing the peptide/allo-major histococompatibility complex.

Generation and adoptive transfusion of alloreactive cytotoxic T lymphocytes (CTLs) specific for tumor are expected to circumvent tumor tolerance. Here we describe a novel protocol to raise allo-restricted, peptide-specific CTLs by co-culture of murine splenocytes and autologous macrophage bearing an allogeneic H-2K molecule associated with its restricted peptide (peptide/allo-MHC). The extracellular domains of H-2K(d) were fused with constant domains of murine IgG2a heavy chain to generate a fusion protein (peptide/H-2K(d)/IgG2aFc, the dimer) consisting of divalent TCR-ligands and an IgG Fc receptor type I (FcgammaRI)-reactive moiety.

[Biocompatibility of combined deproteinized bone coated with hepatocyte growth factor as scaffold for osteoblasts in vitro in fetal rabbits].

Objective: To determine the cellular compatibility of combined deproteinized bone(DPB) coated with hepatocyte growth factor (HGF), and to observe the adherent effect of osteoblasts in response to HGF.

Methods: Osteoblasts were isolated from fetal rabbits. Osteoblasts were cultured with DPB coated with HGF and deproteinized bone as experimental group and contral group, respectively.