Publications by authors named "A Sheih"
Chimeric antigen receptor-modified T cell (CAR-T) immunotherapy has revolutionised blood cancer treatment. Parsing the genetic underpinnings of T cell quality and CAR-T efficacy is challenging. Transcriptomics inform CAR-T state, but the nature of dynamic transcription during activation hinders identification of transiently or minimally expressed genes, such as transcription factors, and over-emphasises effector and metabolism genes.
View Article and Find Full Text PDFBackground: Chimeric antigen receptor (CAR) T-cell therapies have demonstrated transformational outcomes in the treatment of B-cell malignancies, but their widespread use is hindered by technical and logistical challenges associated with ex vivo cell manufacturing. To overcome these challenges, we developed VivoVec, a lentiviral vector-based platform for in vivo engineering of T cells. UB-VV100, a VivoVec clinical candidate for the treatment of B-cell malignancies, displays an anti-CD3 single-chain variable fragment (scFv) on the surface and delivers a genetic payload that encodes a second-generation CD19-targeted CAR along with a rapamycin-activated cytokine receptor (RACR) system designed to overcome the need for lymphodepleting chemotherapy in supporting successful CAR T-cell expansion and persistence.
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- A study of 44 patients receiving a second CAR T-cell infusion (CART2) found low severe toxicity rates and varied complete response rates across different types of B-cell cancers.
- Key findings indicate that certain pretreatment factors, like using specific lymphodepletion methods and increasing doses for the second infusion, can significantly improve patient outcomes and suggest strategies for future CAR T-cell therapy trials.
Article Synopsis
- A pilot study evaluated the concurrent use of ibrutinib with CD19 CAR T-cell therapy in 19 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) after failing ibrutinib treatment.
- The combination therapy was safe and well tolerated, with 68% of patients receiving planned ibrutinib doses and an impressive overall response rate of 83%.
- Patients demonstrated a high rate of minimal residual disease (MRD)-negative responses, and the treatment was associated with reduced severity of cytokine release syndrome (CRS) compared to CAR T-cell therapy alone.
Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, and single-cell RNA sequencing (scRNA-seq) to profile CD8 CAR-T cells from infusion products (IPs) and blood of patients undergoing CD19 CAR-T immunotherapy.
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