Human plasma cells engineered to secrete bispecifics drive effective in vivo leukemia killing.

Bispecific antibodies are an important tool for the management and treatment of acute leukemias. As a next step toward clinical translation of engineered plasma cells, we describe approaches for secretion of bispecific antibodies by human plasma cells. We show that human plasma cells expressing either fragment crystallizable domain-deficient anti-CD19 × anti-CD3 (blinatumomab) or anti-CD33 × anti-CD3 bispecific antibodies mediate T cell activation and direct T cell killing of B acute lymphoblastic leukemia or acute myeloid leukemia cell lines in vitro.

Human plasma cells engineered to secrete bispecifics drive effective leukemia killing.

Bispecific antibodies are an important tool for the management and treatment of acute leukemias. Advances in genome-engineering have enabled the generation of human plasma cells that secrete therapeutic proteins and are capable of long-term engraftment in humanized mouse models. As a next step towards clinical translation of engineered plasma cells (ePCs) towards cancer therapy, here we describe approaches for the expression and secretion of bispecific antibodies by human plasma cells.

Antibody Fc characteristics and effector functions correlate with protection from symptomatic dengue virus type 3 infection.

Preexisting cross-reactive antibodies have been implicated in both protection and pathogenesis during subsequent infections with different dengue virus (DENV) serotypes (DENV1-4). Nonetheless, humoral immune correlates and mechanisms of protection have remained elusive. Using a systems serology approach to evaluate humoral responses, we profiled plasma collected before inapparent or symptomatic secondary DENV3 infection from our pediatric cohort in Nicaragua.

Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine.

Background: Dengue is caused by 4 antigenically distinct serotypes of dengue virus (DENV1-4). Takeda's live attenuated tetravalent dengue vaccine (TAK-003) candidate is composed of an attenuated DENV2 and chimeric viruses containing prM/E of DENV1, 3 and 4 on the DENV2 backbone. The multicolor FluoroSpot (MCF) assay enables quantitation of serotype-specific and cross-reactive individual memory B cells (MBCs) secreting DENV-specific antibodies in a polyclonal mixture.

Primary and Secondary Dengue Virus Infections Elicit Similar Memory B-Cell Responses, but Breadth to Other Serotypes and Cross-Reactivity to Zika Virus Is Higher in Secondary Dengue.

Background: The 4 antigenically distinct serotypes of dengue virus (DENV) share extensive homology with each other and with the closely related Zika flavivirus (ZIKV). The development of polyclonal memory B cells (MBCs) to the 4 DENV serotypes and ZIKV during DENV infection is not fully understood.

Methods: In this study, we analyzed polyclonal MBCs at the single-cell level from peripheral blood mononuclear cells collected ~2 weeks or 6-7 months postprimary or postsecondary DENV infection from a pediatric hospital-based study in Nicaragua using a Multi-Color FluoroSpot assay.

Polygodial analog induces apoptosis in LNCaP prostate cancer cells.

Prostate cancer (PCa) is the second leading cause of death in American men. The chemotherapeutic treatment strategies are generally not effective and can lead to side effects. Hence, there is an urgent need to identify novel chemotherapeutic agents.

Antioxidant Activity of Yichun Blue Honeysuckle (YBHS) Berry Counteracts CCl₄-Induced Toxicity in Liver Injury Model of Mice.

Yichun Blue Honeysuckle (YBHS) is reported to have a broad range of health benefits including protection against a number of chronic diseases. The objective of our study was to determine whether YBHS exhibits antioxidant activity, and if so, determine how it provides protection against oxidative stress. Eight-week old mice (25 male and 25 female) were randomized into five groups ( = 10 per group).