Bluebird Bio (United States)

Abstract Description Some individuals are unable to receive chimeric antigen receptor T cells (CAR-Ts) due to the inability to manufacture their T cells. We hypothesized that a cell-based scaffold that was able to deliver multiple costimulatory and cytokine signals could expand T cells more effectively than current platforms, resulting in the ability for more individuals to benefit from CAR-T therapy. To test this, we generated an array of K562-based aAPCs and found that aAPCs that used an OKT3-based scFv to deliver signal 1, CD86 and 4-1BBL to deliver costimulatory signals and produced IL-7 and IL-15 to provide cytokine support were able to robustly expand T cells. We manufactured cell-derived nanoparticles (CDNPs) from these aAPCs that were able to decrease the time needed for T cells to complete their first cell division compared to synthetic, agonist antibody coated beads and were able to generate highly functional CAR-T cells. Importantly, CDNPs were able to robustly expand T cells from 15 patient donors, including 5 samples that could not be manufactured using state of the art approaches. Lastly, CAR-Ts manufactured by CDNPs, especially those that used an accelerated manufacturing process, were able to eliminate tumors in vivo more effectively than CAR-Ts manufactured by anti-CD3/28 coated beads, providing the basis and rationale to use these CDNPs in the CAR-T manufacturing process. Funding Sources BlueWhale Bio Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)

Particle manipulation plays a pivotal role in scientific and technological domains such as materials science, physics, and the life sciences. Here, we present a dynamically reconfigurable acoustofluidic metasurface that enables precise trapping and positioning of microscale particles in fluidic environments. By harnessing acoustic-structure interaction in a passive membrane resonator array, we generate localized standing acoustic waves that can be reconfigured in real-time. The resulting radiation force allows for subwavelength manipulation and patterning of particles on the metasurface at individual and collective scales, with actuation frequencies below 2 MHz. We further demonstrate the capabilities of the reconfigurable metasurface in trapping and enriching beads and biological cells flowing in microfluidic channels, showcasing its potential in high-throughput bioanalytical applications. Our versatile and biocompatible particle manipulation platform is suitable for applications ranging from the assembly of colloidal particles to enrichment of rare cells.

The COVID-19 pandemic introduced an urgent need for rapid and high-throughput testing for SARS-CoV-2. RNA extraction is a major bottleneck for RT-qPCR. We describe a semi-automated, extraction-free RT-qPCR assay for detection of SARS-CoV-2 in nasal swab and saliva samples on a single platform. With a limit of detection of 4 copies/mL, this laboratory developed test performed equivalently to established methods requiring nucleic acid extraction. Five technologists staffing two shifts per day (80 person-hours) processed more than 400,000 samples over 10 months. Patients opted to provide nasal swab samples (83.6%) more frequently than saliva (16.4%), creating the added challenge of producing swab collection kits. Real-world testing data indicated a higher frequency of SARS-CoV-2 detection in saliva (10.1%) compared to nasal swab (7.7%). This cost-effective and quickly scalable approach is suitable for pandemic preparedness planning related to surveillance and diagnostic testing.

Diaphorina citri is a serious insect pest of citrus and an insect vector of Candidatus Liberibacter asiaticus (CLas) that causes Huanglongbing disease (citrus greening). In this study, we investigated the effect of the CLas pathogen on the life history parameters of D. citri at different temperature regimes. Our results demonstrated that the survival rate of first to fifth instar CLas-positive and CLas-negative D. citri fluctuate with the change in temperature over the range of 16–35 °C. Meanwhile, the mean developmental time (52.5 d) (d = day(s)) and adult longevity (5.2 d) of the CLas-positive psyllids was longer as compared to CLas-negative psyllids mean developmental time (32.81 d) and adult longevity (3.50 d) at the low- and high-temperature regimes (16 and 35 °C). However, at high temperature regimes, the significant effect of CLas-bacteria on D. citri fecundity was higher than the corresponding non-significant effect on their survivorship when compared to non-vectored psyllids. These results indicate a long-term, stable evolutionary relationship among vector-pathogen and climate change.

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