Efficient manufacturing of CAR-T cells from whole blood: a scalable approach to reduce costs and enhance accessibility in cancer therapy.

Background: Chimeric antigen receptor T (CAR-T) cells have significantly advanced the treatment of cancers such as leukemia and lymphoma. Traditionally, T cells are collected from patients through leukapheresis, an expensive and potentially invasive process that requires specialized equipment and trained personnel. Although whole blood collections are much more technically straightforward, whole blood starting material has not been widely utilized for clinical CAR-T cell manufacturing, in part due to lack of manufacturing processes designed for use in a good manufacturing practice (GMP) environment.

Overcoming the challenges of primary resistance and relapse after CAR-T cell therapy.

Introduction: While CAR T-cell therapy has led to remarkable responses in relapsed B-cell hematologic malignancies, only 50% of patients ultimately have a complete, sustained response. Understanding the mechanisms of resistance and relapse after CAR T-cell therapy is crucial to future development and improving outcomes.

Areas Covered: We review reasons for both primary resistance and relapse after CAR T-cell therapies.

Deciphering the importance of culture pH on CD22 CAR T-cells characteristics.

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.

Emerging Biomarkers for Monitoring Chimeric Antigen Receptor T-Cell Therapy.

Background: Chimeric antigen receptor (CAR) T-cell therapy has revolutionized treatment of hematologic malignancies and holds promise for solid tumors. While responses to CAR T-cell therapy have surpassed other available options for patients with refractory malignancies, not all patients respond the same way. The reason for this variability is not currently understood.

HLH-like toxicities predict poor survival after the use of tisagenlecleucel in children and young adults with B-ALL.

Chimeric antigen receptor-associated hemophagocytic lymphohistiocytosis (HLH)-like toxicities (LTs) involving hyperferritinemia, multiorgan dysfunction, coagulopathy, and/or hemophagocytosis are described as occurring in a subset of patients with cytokine release syndrome (CRS). Case series report poor outcomes for those with B-cell acute lymphoblastic leukemia (B-ALL) who develop HLH-LTs, although larger outcomes analyses of children and young adults (CAYAs) with B-ALL who develop these toxicities after the administration of commercially available tisagenlecleucel are not described. Using a multi-institutional database of 185 CAYAs with B-ALL, we conducted a retrospective cohort study including groups that developed HLH-LTs, high-grade (HG) CRS without HLH-LTs, or no to low-grade (NLG) CRS without HLH-LTs.

Cryopreserved anti-CD22 and bispecific anti-CD19/22 CAR T cells are as effective as freshly infused cells.

Cryopreservation of chimeric antigen receptor (CAR) T cells facilitates shipment, timing of infusions, and storage of subsequent doses. However, reports on the impact of cryopreservation on CAR T cell efficacy have been mixed. We retrospectively compared clinical outcomes between patients who received cryopreserved versus fresh CAR T cells for treatment of B cell leukemia across two cohorts of pediatric and young adult patients: those who received anti-CD22 CAR T cells and those who received bispecific anti-CD19/22 CAR T cells.

Impact of PCV-13 vaccine on invasive pneumococcal disease in hospitalised children: A multi-institutional analysis.

Aim: We aimed to describe changes in invasive pneumococcal disease (IPD) hospitalisations after introduction of the pneumococcal conjugate vaccine (PCV13).

Methods: This was a retrospective analysis of the Pediatric Health Information System (PHIS) database, including children with IPD pre-PCV13 (2004-2009) and post-PCV13 (2012-2017). Healthy children and those with chronic conditions were analysed separately.

Adolescent and young adult oncology-past, present, and future.

There are nearly 70,000 new cancer diagnoses made annually in adolescents and young adults (AYAs) in the United States. Historically, AYA patients with cancer, aged 15 to 39 years, have not shown the same improved survival as older or younger cohorts. This article reviews the contemporary cancer incidence and survival data through 2015 for the AYA patient population based on the National Cancer Institute's Surveillance, Epidemiology, and End Results registry program and the North American Association of Central Cancer Registries.

Outcomes and swallowing evaluations after injection laryngoplasty for type I laryngeal cleft: Does age matter?

Objectives: To improve the recognition of differences in presentation amongst patients with type 1 laryngeal clefts of various ages and better understand the age dependent outcomes of injection laryngoplasty. A second aim was to analyze the discrepancies between swallow assessment modalities in various age groups with type I laryngeal clefts undergoing injection laryngoplasty.

Methods: A retrospective review of electronic medical records of patients who underwent injection laryngoplasty from 2009 through 2015 at a tertiary care children's hospital.

Host conditioning and rejection monitoring in hepatocyte transplantation in humans.

Background & Aims: Hepatocyte transplantation partially corrects genetic disorders and has been associated anecdotally with reversal of acute liver failure. Monitoring for graft function and rejection has been difficult, and has contributed to limited graft survival. Here we aimed to use preparative liver-directed radiation therapy, and continuous monitoring for possible rejection in an attempt to overcome these limitations.

Long-term outcomes and predictors in pediatric liver retransplantation.

Historically, 9-29% of pediatric liver transplant recipients have required retransplantation. Although outcomes have improved over the last decade, currently published patient and graft survival remain lower after retransplant than after primary transplant. Data from liver retransplantation recipients at our institution between 1991 and 2013 were retrospectively reviewed.

Parent perspectives on decisions to participate in a phase I hepatocyte transplant trial.

We examined factors that affect decision-making for families presented with a phase I clinical trial of hepatocyte transplant as a potential alternative to liver transplant for their children among two groups: (i) families who were actually offered enrollment in the hepatocyte trial and; (ii) families whose children had liver transplants before the trial was available. We conducted semi-structured interviews about actual and hypothetical decision-making regarding trial participation and used grounded theory analysis to identify common themes. The most common motivator for participation was decline in the child's health.

Induction of erythropoiesis using human vascular networks genetically engineered for controlled erythropoietin release.

For decades, autologous ex vivo gene therapy has been postulated as a potential alternative to parenteral administration of recombinant proteins. However, achieving effective cellular engraftment of previously retrieved patient cells is challenging. Recently, our ability to engineer vasculature in vivo has allowed for the introduction of instructions into tissues by genetically modifying the vascular cells that build these blood vessels.

Functional endothelial progenitor cells from cryopreserved umbilical cord blood.

Umbilical cord blood (UCB) is recognized as an enriched source of endothelial progenitor cells (EPCs) with potential therapeutic value. Because cryopreservation is the only reliable method for long-term storage of UCB cells, the clinical application of EPCs depends on our ability to acquire them from cryopreserved samples; however, the feasibility of doing so remains unclear. In this study we demonstrate that EPCs can be isolated from cryopreserved UCB-derived mononuclear cells (MNCs).