Allogeneic B cell immunomodulatory therapy in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is an orphan neurodegenerative disease. Immune system dysregulation plays an essential role in ALS onset and progression. Our preclinical studies have shown that the administration of exogenous allogeneic B cells improves outcomes in murine models of skin and brain injury through a process termed pligodraxis, in which B cells adopt an immunoregulatory and neuroprotective phenotype in an injured environment.

Novel Autologous Dendritic Cell Therapy AVT001 for Type 1 Diabetes.

Background: CD8+ T regulatory (Treg) cells that recognize the nonclassical class 1b molecule Qa-1/human leukocyte antigen E (Q/E CD8+ Treg cells) are important in maintaining self-tolerance. We sought to investigate the role that these T cells play in type 1 diabetes (T1D) pathogenesis and whether an intervention targeting this mechanism may delay T1D progression.

Methods: We conducted a phase 1/2, randomized, double-blind, placebo-controlled trial of the autologous dendritic cell therapy AVT001 that included participants at least 16 years of age, within 1 year of T1D diagnosis, and with ex vivo evidence of a defect in Q/E CD8+ Treg function.

Evaluation of Maternal-Fetal Medicine Fellowship Program Websites.

Introduction Due to the COVID-19 pandemic, the American Association of Medical Colleges (AAMC) recommended that all interviews for residencies and fellowships be conducted in a virtual format. As of March 2024, the Society of Maternal-Fetal Medicine (SMFM) continues to request that all fellowship interviews occur virtually. Without in-person interviews, prospective Maternal-Fetal Medicine (MFM) fellowship applicants must largely rely on program websites to gain insight into each program's offerings, culture, and application requirements.

Phase II trial of vaccination with autologous, irradiated melanoma cells engineered by adenoviral mediated gene transfer to secrete granulocyte-macrophage colony stimulating factor in patients with stage III and IV melanoma.

Background: In the era of immune checkpoint blockade, the role of cancer vaccines in immune priming has provided additional potential for therapeutic improvements. Prior studies have demonstrated delayed type hypersensitivity and anti-tumor immunity with vaccines engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF). The safety, efficacy and anti-tumor immunity of GM-CSF secreting vaccine in patients with previously treated stage III or IV melanoma needs further investigation.

Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies.

We report a first-in-human clinical trial using chimeric antigen receptor (CAR) T cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies. Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T cells. CAR-37 T cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4 of 5 patients.

A phase 1/2 clinical trial of invariant natural killer T cell therapy in moderate-severe acute respiratory distress syndrome.

Invariant natural killer T (iNKT) cells, a unique T cell population, lend themselves for use as adoptive therapy due to diverse roles in orchestrating immune responses. Originally developed for use in cancer, agenT-797 is a donor-unrestricted allogeneic ex vivo expanded iNKT cell therapy. We conducted an open-label study in virally induced acute respiratory distress syndrome (ARDS) caused by the severe acute respiratory syndrome-2 virus (trial registration NCT04582201).

Cultivated autologous limbal epithelial cell (CALEC) transplantation: Development of manufacturing process and clinical evaluation of feasibility and safety.

To treat unilateral limbal stem cell (LSC) deficiency, we developed cultivated autologous limbal epithelial cells (CALEC) using an innovative xenobiotic-free, serum-free, antibiotic-free, two-step manufacturing process for LSC isolation and expansion onto human amniotic membrane with rigorous quality control in a good manufacturing practices facility. Limbal biopsies were used to generate CALEC constructs, and final grafts were evaluated by noninvasive scanning microscopy and tested for viability and sterility. Cultivated cells maintained epithelial cell phenotype with colony-forming and proliferative capacities.

The feasibility of using an autologous GM-CSF-secreting breast cancer vaccine to induce immunity in patients with stage II-III and metastatic breast cancers.

Purpose: The antigenic targets of immunity and the role of vaccination in breast cancer are unknown. We performed a phase I study of an autologous GM-CSF-secreting breast cancer vaccine in patients with metastatic and stage II-III breast cancer.

Methods: Tumor cells from patients with metastatic (n = 15) and stage II-III (n = 7) disease were transduced with a replication-defective adenoviral vector encoding GM-CSF, and then irradiated.

Phase 1 study of CART-ddBCMA for the treatment of subjects with relapsed and refractory multiple myeloma.

Relapsed and refractory multiple myeloma (RRMM) is a plasma cell neoplasm defined by progressively refractory disease necessitating chronic and increasingly intensive therapy. Despite recent advances, limited treatment options exist for RRMM. This single-arm, open label phase 1 study aimed to evaluate the safety of novel B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T construct that leverages a completely synthetic antigen-binding domain (CART-ddBCMA), which was specifically engineered to reduce immunogenicity and improve CAR cell surface stability.

GM-CSF secreting leukemia cell vaccination for MDS/AML after allogeneic HSCT: a randomized, double-blinded, phase 2 trial.

Vaccination using irradiated, adenovirus transduced autologous myeloblasts to secrete granulocyte-macrophage colony-stimulating factor (GVAX) early after allogeneic hematopoietic stem cell transplantation (HSCT) can induce potent immune responses. We conducted a randomized phase 2 trial of GVAX after HSCT for myelodysplastic syndrome with excess blasts or relapsed/refractory acute myeloid leukemia. Myeloblasts were harvested before HSCT to generate the vaccine.

Post-Transcriptional Genetic Silencing of to Treat Sickle Cell Disease.

Background: Sickle cell disease is characterized by hemolytic anemia, pain, and progressive organ damage. A high level of erythrocyte fetal hemoglobin (HbF) comprising α- and γ-globins may ameliorate these manifestations by mitigating sickle hemoglobin polymerization and erythrocyte sickling. is a repressor of γ-globin expression and HbF production in adult erythrocytes.

Intracranial injuries on computed tomography head scans in infants investigated for suspected physical abuse: a retrospective review.

Background: UK national guidelines recommend that investigation of infants (aged <12 months) with suspected physical abuse should always include CT head scans. Such imaging carries small but recognised risks from radiation exposure. Studies report a range of yields for occult intracranial injuries in suspected physical abuse.

Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial.

Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses and can function as bona fide antigens that facilitate tumour rejection. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load and an immunologically 'cold' tumour microenvironment. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study.

Phase I Trial of Autologous CAR T Cells Targeting NKG2D Ligands in Patients with AML/MDS and Multiple Myeloma.

NKG2D ligands are widely expressed in solid and hematologic malignancies but absent or poorly expressed on healthy tissues. We conducted a phase I dose-escalation study to evaluate the safety and feasibility of a single infusion of NKG2D-chimeric antigen receptor (CAR) T cells, without lymphodepleting conditioning in subjects with acute myeloid leukemia/myelodysplastic syndrome or relapsed/refractory multiple myeloma. Autologous T cells were transfected with a γ-retroviral vector encoding a CAR fusing human NKG2D with the CD3ζ signaling domain.

Successful hematopoietic stem cell mobilization and apheresis collection using plerixafor alone in sickle cell patients.

Novel therapies for sickle cell disease (SCD) based on genetically engineered autologous hematopoietic stem and progenitor cells (HSPCs) are critically dependent on a safe and effective strategy for cell procurement. We sought to assess the safety and efficacy of plerixafor when used in transfused patients with SCD for HSC mobilization. Six adult patients with SCD were recruited to receive a single dose of plerixafor, tested at lower than standard (180 µg/kg) and standard (240 µg/kg) doses, followed by CD34 cell monitoring in peripheral blood and apheresis collection.

Manufacturing development and clinical production of NKG2D chimeric antigen receptor-expressing T cells for autologous adoptive cell therapy.

Background Aims: Adoptive cell therapy employing natural killer group 2D (NKG2D) chimeric antigen receptor (CAR)-modified T cells has demonstrated preclinical efficacy in several model systems, including hematological and solid tumors. We present comprehensive data on manufacturing development and clinical production of autologous NKG2D CAR T cells for treatment of acute myeloid leukemia and multiple myeloma (ClinicalTrials.gov Identifier: NCT02203825).

Corrigendum: An immunogenic personal neoantigen vaccine for patients with melanoma.

This corrects the article DOI: 10.1038/nature22991.

Vaccination with autologous myeloblasts admixed with GM-K562 cells in patients with advanced MDS or AML after allogeneic HSCT.

We report a clinical trial testing vaccination of autologous myeloblasts admixed with granulocyte-macrophage colony-stimulating factor secreting K562 cells after allogeneic hematopoietic stem cell transplantation (HSCT). Patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with ≥5% marrow blasts underwent myeloblast collection before HSCT. At approximately day +30, 6 vaccines composed of irradiated autologous myeloblasts mixed with GM-K562 were administered.

An immunogenic personal neoantigen vaccine for patients with melanoma.

Effective anti-tumour immunity in humans has been associated with the presence of T cells directed at cancer neoantigens, a class of HLA-bound peptides that arise from tumour-specific mutations. They are highly immunogenic because they are not present in normal tissues and hence bypass central thymic tolerance. Although neoantigens were long-envisioned as optimal targets for an anti-tumour immune response, their systematic discovery and evaluation only became feasible with the recent availability of massively parallel sequencing for detection of all coding mutations within tumours, and of machine learning approaches to reliably predict those mutated peptides with high-affinity binding of autologous human leukocyte antigen (HLA) molecules.

Epstein-Barr virus-specific adoptive immunotherapy for recurrent, metastatic nasopharyngeal carcinoma.

Background: Early-stage and intermediate-stage nasopharyngeal cancer (NPC) generally carry a good prognosis, but for patients with recurrent, metastatic disease, options are limited. In the current study, the authors present a phase 1/2 study to evaluate the efficacy of Epstein-Barr virus (EBV)-stimulated cytotoxic T-lymphocyte (EBV-CTL) immunotherapy in this patient population.

Methods: Screening for patients with active, recurrent, metastatic EBV-associated NPC began in February 2007, and the study was closed to accrual in January 2012.

Adoptive Transfer of Invariant NKT Cells as Immunotherapy for Advanced Melanoma: A Phase I Clinical Trial.

Invariant NKT cells (iNKT) are innate-like CD1d-restricted T cells with immunoregulatory activity in diseases including cancer. iNKT from advanced cancer patients can have reversible defects including IFNγ production, and iNKT IFNγ production may stratify for survival. Previous clinical trials using iNKT cell activating ligand α-galactosylceramide have shown clinical responses.

Time of Day and Training Status Both Impact the Efficacy of Caffeine for Short Duration Cycling Performance.

This project was designed to assess the effects of time of day and training status on the benefits of caffeine supplementation for cycling performance. Twenty male subjects (Age, 25 years; Peak oxygen consumption, 57 mL·kg·min) were divided into tertiles based on training levels, with top and bottom tertiles designated as 'trained' ( = 7) and 'untrained' ( = 7). Subjects completed two familiarization trials and four experimental trials consisting of a computer-simulated 3-km cycling time trial (TT).

A phase I study of CD25/regulatory T-cell-depleted donor lymphocyte infusion for relapse after allogeneic stem cell transplantation.

Donor lymphocyte infusions are used to treat relapse after allogeneic hematopoietic stem cell transplantation, but responses are inadequate. In addition to effector cells, infusions contain CD25 regulatory T cells (Treg) that may suppress graft-versus-tumor responses. We undertook a phase I study of donor lymphocyte infusions depleted of CD25 T cells in patients with hematologic malignancies who had relapsed after transplantation.

High density electromyography data of normally limbed and transradial amputee subjects for multifunction prosthetic control.

Pattern recognition based control of powered upper limb myoelectric prostheses offers a means of extracting more information from the available muscles than conventional methods. By identifying repeatable patterns of muscle activity across multiple muscle sites rather than relying on independent EMG signals it is possible to provide more natural, reliable control of myoelectric prostheses. The purposes of this study were to (1) determine if participants can perform distinctive muscle activation patterns associated with multiple wrist and hand movements reliably and (2) to show that high density EMG can be applied individually to determine the electrode location of a clinically acceptable number of electrodes (maximally eight) to classify multiple wrist and hand movements reliably in transradial amputees.