Publications by authors named "Lipei Shao"

Although CAR T-cell therapy is increasingly used to treat relapsed B-cell acute lymphoblastic leukemia (ALL), 20-30% of patients do not respond, and few clinical predictors of response have been established, especially in the pediatric population. A deeper analysis of CAR T-cell infusion products, along with the apheresis product used as the starting material for CAR T-cell manufacturing, provides valuable insights for predicting clinical outcomes. We analyzed infusion products and CD4/8-selected T-cell starting materials from pediatric and young adult patients on a single-center study with relapsed/refractory B-cell ALL who were undergoing treatment with CD22 CAR T-cells and evaluated differences between T-cells from responders and non-responders (NCT023215612).

View Article and Find Full Text PDF
Article Synopsis
  • A study was conducted to compare a new DMSO-free cryoprotectant solution with traditional DMSO solutions for freezing mesenchymal stem/stromal cells (MSCs) to prevent cell toxicity and ensure safe clinical use.
  • The new solution, made of sucrose, glycerol, and isoleucine, was tested against 5-10% DMSO solutions prepared by seven different centers, focusing on the viability and recovery of MSCs after thawing.
  • Results showed that while the average viability of MSCs decreased with both solutions post-cryopreservation, the DMSO-free solution displayed a more significant reduction in cell viability compared to the traditional DMSO solutions, highlighting its potential benefits for
View Article and Find Full Text PDF

T cell activation is an essential step in chimeric Ag receptor (CAR) T (CAR T) cell manufacturing and is accomplished by the addition of activator reagents that trigger the TCR and provide costimulation. We explore several T cell activation reagents and examine their effects on key attributes of CAR T cell cultures, such as activation/exhaustion markers, cell expansion, gene expression, and transduction efficiency. Four distinct activators were examined, all using anti-CD3 and anti-CD28, but incorporating different mechanisms of delivery: Dynabeads (magnetic microspheres), TransAct (polymeric nanomatrix), Cloudz (alginate hydrogel), and Microbubbles (lipid membrane containing perfluorocarbon gas).

View Article and Find Full Text PDF

Background: Chimeric antigen receptor (CAR) T-cells have demonstrated significant efficacy in targeting hematological malignancies, and their use continues to expand. Despite substantial efforts spent on the optimization of protocols for CAR T-cell manufacturing, critical parameters of cell culture such as pH or oxygenation are rarely actively monitored during cGMP CAR T-cell generation. A comprehensive understanding of the role that these factors play in manufacturing may help in optimizing patient-specific CAR T-cell therapy with maximum benefits and minimal toxicity.

View Article and Find Full Text PDF

With investigators looking to expand engineered T cell therapies such as CAR-T to new tumor targets and patient populations, a variety of cell manufacturing platforms have been developed to scale manufacturing capacity using closed and/or automated systems. Such platforms are particularly useful for solid tumor targets, which typically require higher CAR-T cell doses. Although T cell phenotype and function are key attributes that often correlate with therapeutic efficacy, how manufacturing platforms influence the final CAR-T cell product is currently unknown.

View Article and Find Full Text PDF

Chimeric antigen receptor T cells (CART) have demonstrated curative potential for hematological malignancies, but the optimal manufacturing has not yet been determined and may differ across products. The first step, T cell selection, removes contaminating cell types that can potentially suppress T cell expansion and transduction. While positive selection of CD4/CD8 T cells after leukapheresis is often used in clinical trials, it may modulate signaling cascades downstream of these co-receptors; indeed, the addition of a CD4/CD8-positive selection step altered CD22 CART potency and toxicity in patients.

View Article and Find Full Text PDF
Article Synopsis
  • Multiple myeloma (MM) is a challenging cancer of plasma cells, and researchers developed a new treatment using a human anti-BCMA CAR called FHVH33-CD8BBZ to target it.
  • In a clinical trial involving 25 patients with relapsed MM, the treatment resulted in a 52% stringent complete response rate and a median progression-free survival of 78 weeks.
  • While some patients experienced cytokine-release syndrome, it was manageable and most anti-MM effects were observed within 2-4 weeks post-infusion, indicating the treatment's rapid and effective action against the disease.
View Article and Find Full Text PDF

Background Aims: Reference genes are an essential part of clinical assays such as droplet digital polymerase chain reaction (ddPCR), which measure the number of copies of vector integrated into genetically engineered cells and the loss of plasmids in reprogrammed cells used in clinical cell therapies. Care should be taken to select reference genes, because it has been discovered that there may be thousands of variations in copy number from genomic segments among different individuals. In addition, within the same person in the context of cancer and other proliferative disorders, substantial parts of the genome also can differ in copy number between cells from diseased and healthy people.

View Article and Find Full Text PDF

Background: SARS-CoV2 can induce a strong host immune response. Many studies have evaluated antibody response following SARS-CoV2 infections. This study investigated the immune response and T cell receptor diversity in people who had recovered from SARS-CoV2 infection (COVID-19).

View Article and Find Full Text PDF

Background: Clinical CAR T-cell therapy using integrating vector systems represents a promising approach for the treatment of hematological malignancies. Lentiviral and γ-retroviral vectors are the most commonly used vectors in the manufacturing process. However, the integration pattern of these viral vectors and subsequent effect on CAR T-cell products is still unclear.

View Article and Find Full Text PDF

Background: Cytokine release syndrome (CRS) is a strong immune system response that can occur as a result of the reaction of a cellular immunotherapy with malignant cells. While the frequency and management of CRS in CAR T-cell therapy has been well documented, there is emerging interest in pre-emptive treatment to reduce CRS severity and improve overall outcomes. Accordingly, identification of genomic determinants that contribute to cytokine release may lead to the development of targeted therapies to prevent or abrogate the severity of CRS.

View Article and Find Full Text PDF
Article Synopsis
  • CD19 CAR T-cell therapy is effective for B cell cancers but faces challenges like relapse and varying patient responses.
  • The study explored how the bone marrow microenvironment's transcriptomic profile can influence outcomes of the therapy, identifying key genetic signatures tied to clinical remission.
  • It was found that patients who responded well had higher activity in T cell activation pathways, while non-responders showed increased activity in cell cycle checkpoints, suggesting enhancing pro-inflammatory signals in the bone marrow could improve therapy efficacy.
View Article and Find Full Text PDF

Rare germline variations contribute to the missing heritability of human complex diseases including cancers. Given their very low frequency, discovering and testing disease-causing rare germline variations remains challenging. The tag-single nucleotide polymorphism rs17728461 in 22q12.

View Article and Find Full Text PDF

Background: Gene transfer is an important tool for cellular therapies. Lentiviral vectors are most effectively transferred into lymphocytes or hematopoietic progenitor cells using spinoculation. To enable cGMP (current Good Manufacturing Practice)-compliant cell therapy production, we developed and compared a closed-system spinoculation method that uses cell culture bags, and an automated closed system spinoculation method to decrease technician hands on time and reduce the likelihood for microbial contamination.

View Article and Find Full Text PDF
Article Synopsis
  • CAR T-cell therapy can cause a severe side effect known as chimeric antigen receptor-associated hemophagocytic lymphohistiocytosis (carHLH), which is linked to cytokine release syndrome (CRS) in some patients.
  • In a study of 59 patients who received CD22 CAR T cells, about 40% developed carHLH, showing symptoms like high ferritin levels, liver issues, and low white blood cell counts.
  • The development of carHLH is associated with pre-existing low levels of natural killer (NK) cells and higher ratios of T cells to NK cells in the bone marrow, especially after CAR T-cell expansion, indicating a need for better identification and management strategies for this condition
View Article and Find Full Text PDF

Background: Genetically engineered T cells have become an important therapy for B-cell malignancies. Measuring the efficiency of vector integration into the T cell genome is important for assessing the potency and safety of these cancer immunotherapies.

Methods: A digital droplet polymerase chain reaction (ddPCR) assay was developed and evaluated for assessing the average number of lenti- and retroviral vectors integrated into Chimeric Antigen Receptor (CAR) and T Cell Receptor (TCR)-engineered T cells.

View Article and Find Full Text PDF

Background: Inherited factors contribute to lung cancer risk, but the mechanism is not well understood. Defining the biological consequence of GWAS hits in cancers is a promising strategy to elucidate the inherited mechanisms of cancers. The tag-SNP rs753955 (A>G) in 13q12.

View Article and Find Full Text PDF

Breast cancer is a common malignancy in women. Acquisition of drug resistance is one of the main obstacles encountered in breast cancer therapy. Long non-coding RNA (lncRNA) has been demonstrated to play vital roles in both development and tumorigenesis.

View Article and Find Full Text PDF

Drug-induced aberrant DNA methylation is the first identified epigenetic marker involved in chemotherapy resistance. Understanding how the aberrant DNA methylation is acquired would impact cancer treatment in theory and practice. In this study we systematically investigated whether and how ERα propelled aberrant global DNA hypermethylation in the context of breast cancer drug resistance.

View Article and Find Full Text PDF

Aberrant expression of special AT-rich binding protein 1 (SATB1), a global genomic organizer, has been associated with various cancers, which raises the question of how higher-order chromatin structure contributes to carcinogenesis. Disruption of apoptosis is one of the hallmarks of cancer. We previously demonstrated that SATB1 mediated specific long-range chromosomal interactions between the mbr enhancer located within 3'-UTR of the BCL2 gene and the promoter to regulate BCL2 expression during early apoptosis.

View Article and Find Full Text PDF

A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session1ie66umrtq53q3ucdsddmtb194988oaj): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once