Neurotoxicity and Rare Adverse Events in BCMA-Directed CAR T Cell Therapy: A Comprehensive Analysis of Real-World FAERS Data.

Chimeric antigen receptor T (CAR T) cell therapies have emerged as a valuable treatment modality for patients with plasma cell disorders. As the population of patients receiving CAR T therapies grows, the identification and management of associated rare toxicities become increasingly crucial. This study aims to identify safety signals associated with commercial anti-B-cell maturation antigen (BCMA) CAR T therapies using the Food and Drug Administration Adverse Event Reporting System (FAERS).

ACT To Sustain: Adoptive Cell Therapy To Sustain Access to Non-Commercialized Genetically Modified Cell Therapies.

Genetically modified cell therapies (GMCT), particularly immune effector cells (IEC) such as chimeric receptor antigen (CAR) T cells, have shown promise in curing cancer and rare diseases after a single treatment course. Following close behind CAR T approvals are GMCT based on hematopoietic stem cells, such as products developed for hemoglobinopathies and other disorders. Academically sponsored GMCT products, often developed in academic centers without industry involvement, face challenges in sustaining access after completion of early phase studies when there is no commercial partner invested in completing registration trials for marketing applications.

National Survey of FACT-Accredited Cell Processing Facilities: Assessing Preparedness for Local Manufacturing of Immune Effector Cells.

The utilization of the human immune system as a therapeutic modality has materialized in the form of novel biologics known as immune effector cells (IECs). However, currently approved IECs rely on autologous cells for manufacturing that are funneled through costly centralized supply chains leading to long wait times and potentially increased mortality. Alternative models for manufacturing at or near the point-of-care in a distributed and local approach are being proposed to overcome such a bottleneck.

Second primary malignancies after commercial CAR T-cell therapy: analysis of the FDA Adverse Events Reporting System.

Second primary malignancies were reported in 536 of 12 394 (4.3%) adverse event reports following chimeric antigen receptor T-cell therapies in the Food and Drug Administration Adverse Event Reporting System. Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up.

Expanding access to CAR T cell therapies through local manufacturing.

Chimeric antigen receptor (CAR) T cells are changing the therapeutic landscape for hematological malignancies. To date, all six CAR T cell products approved by the US Food and Drug Administration (FDA) are autologous and centrally manufactured. As the numbers of approved products and indications continue to grow, new strategies to increase cell-manufacturing capacity are urgently needed to ensure patient access.

CAR NK-92 cell-mediated depletion of residual TCR+ cells for ultrapure allogeneic TCR-deleted CAR T-cell products.

Graft-versus-host disease (GVHD) is a major risk of the administration of allogeneic chimeric antigen receptor (CAR)-redirected T cells to patients who are HLA unmatched. Gene editing can be used to disrupt potentially alloreactive T-cell receptors (TCRs) in CAR T cells and reduce the risk of GVHD. Despite the high knockout rates achieved with the optimized methods, a subsequent purification step is necessary to obtain a safe allogeneic product.

Long-term response to autologous anti-CD19 chimeric antigen receptor T cells in relapsed or refractory B cell acute lymphoblastic leukemia: a systematic review and meta-analysis.

Chimeric Antigen Receptor (CAR) T cell therapy is an effective treatment approach for patients with relapsed or refractory acute lymphoblastic leukemia (R/R B-ALL). However, identifying the factors that influence long-term response to this therapy is necessary to optimize patient selection and treatment allocation. We conducted a literature review and meta-analysis to investigate the use of autologous anti-CD19 CAR T cell therapy in both pediatric and adult patients with R/R B-ALL, using several databases including MEDLINE, Cochrane Central, ScienceDirect, Web of Science, Journals@Ovid, Embase, and clinicaltrial.

Scalable Manufacturing of CAR T cells for Cancer Immunotherapy.

Unlabelled: As of April 2021, there are five commercially available chimeric antigen receptor (CAR) T cell therapies for hematological malignancies. With the current transition of CAR T cell manufacturing from academia to industry, there is a shift toward Good Manufacturing Practice (GMP)-compliant closed and automated systems to ensure reproducibility and to meet the increased demand for cancer patients. In this review we describe current CAR T cells clinical manufacturing models and discuss emerging technological advances that embrace scaling and production optimization.

Mitigating Deficiencies in Evidence during Regulatory Assessments of Advanced Therapies: A Comparative Study with Other Biologicals.

Advanced therapy medicinal products (ATMPs) comprising cell therapy, gene therapy, and tissue-engineered products, offer a multitude of novel therapeutic approaches to a wide range of severe and debilitating diseases. To date, several advanced therapies have received marketing authorization for a variety of indications. However, some products showed disappointing market performance, leading to their withdrawal.

CAR T-cell product performance in haematological malignancies before and after marketing authorisation.

Chimeric antigen receptor (CAR) T cells represent a potent new approach to treat haematological malignancies. Two CAR T-cell therapies, tisagenlecleucel and axicabtagene ciloleucel, have been approved in Europe and the USA, as well as several other countries, for the treatment of leukaemia and lymphoma. These approvals marked a major milestone in the field of cell and gene therapies.

Linking Scattered Stem Cell-Based Data to Advance Therapeutic Development.

The biomedical field has witnessed remarkable advances in analytical tools and technologies that have expanded our understanding of healthy and diseased human tissue and, at the same time, enable extensive molecular characterization of living cells. The volume of scientific data generated is expanding in an unprecedented manner; however, these data remain scattered across research groups worldwide. Access to various data sources in a systematic fashion could hugely benefit the progress of nascent fields such as stem cell-based therapeutics.