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Publications
CD34 Cells, NKT Cells
Stem cell engineering for the generation of allogeneic CAR-directed natural killer T cells targeting endometrial carcinoma
Allogeneic mesothelin-targeting CAR-NKT cells were generated from engineered HSPCs with ex vivo differentiation. They killed uterine endometrial carcinoma cells plus CD1d+ TAMs and MDSCs, with no GvHD and minimal CRS. Scalable systems such as G-REX are named as a next GMP step.
Publications
T-Cells
IL-21-reprogrammed Vδ1 T cells exert killing against solid tumors which is enhanced by CAR arming for off-the-shelf immunotherapy
K562 feeder cells expressing membrane-bound IL-21 preferentially expand Vd1 gamma delta T cells from blood. The cells gain NK activation receptors and kill breast and ovarian tumors, with CAR arming improving efficacy in xenografts. PBMCs were seeded in 24-well G-Rex plates for expansion.
Publications
NK Cells
Pre-clinical characterization and process development of a BCMA-directed CAR NK-cell therapy product for relapsed/refractory multiple myeloma
Primary NK cells from blood, buffy coats and cord blood expanded 30-40x in nine days. An anti-BCMA CAR was delivered as mRNA by LNP, feeder- and virus-free, and the cells killed BCMA+ myeloma lines. Process development scales production in G-Rex bioreactors to about 800 million cells per dose.
Publications
Treg Cells
HLA-A2 CAR/IL-2-CISC engineered Treg display robust in vitro and in vivo antigen-specific regulatory function
HDR editing at the FOXP3 locus created A2CAR engineered Treg carrying an inducible IL-2 signaling complex. The cells kept a Treg phenotype, stayed minimally cytotoxic, and beat polyclonal EngTreg in a xenogeneic GvHD model. Expansion used G-Rex gas-permeable culture systems.
Publications
CAR T Cells
Preclinical development of an optimized manufacturing, CRISPR-edited, fully non-viral 1XX-enhanced anti-BCMA CAR-T therapy for multiple myeloma
A fully non-viral, CRISPR-edited anti-BCMA CAR-T uses TRAC integration and a 1XX CD3z domain. It cleared tumors in myeloma xenografts and outperformed ide-cel and cilta-cel constructs. Manufacturing ran under GMP-compatible conditions with MaxCyte electroporation and G-Rex expansion.
Publications
TCR T Cells
A TGF-βR/IL-2R immunomodulatory fusion protein transforms immunosuppression into T cell activation to enhance adoptive T cell therapy
Chimeric TGF-betaR/IL-2R fusion proteins convert suppressive TGF-beta signals into IL-2 proliferative signals. Engineered CD8+ T cells kept stemness and killed tumors better when paired with a mesothelin TCR. Transduced cells were moved to G-Rex gas-permeable 24-well vessels to expand.
Publications
CAR T Cells
CAR T cell engineering impacts antigen-independent activation and co-inhibition
Lentiviral and non-viral Sleeping Beauty manufacturing were compared for R110- and CD19-CAR T cells. Transposon products shifted to CD8+ subsets with activation and co-inhibition markers and inflammatory nucleotide-sensing signatures. Both arms were expanded in G-Rex 24-well vessels.
Publications
CAR T Cells
TSCM-predominant allogeneic anti-BCMA CAR-T therapy for relapsed/refractory multiple myeloma: preclinical characterization and interim results from a phase 1 trial
P-BCMA-ALLO1 is an allogeneic anti-BCMA CAR-T therapy with a TSCM-predominant phenotype. Preclinical lots and interim phase 1 data in relapsed/refractory myeloma showed 82% response with enhanced lymphodepletion. After electroporation, cells were pooled and cultured overnight in a G-Rex vessel.
