Transcriptome profiling reveals distinct alterations in the B-cell signature and dysregulation of peripheral B-cell subsets in sickle cell anemia patients.

Sickle cell anemia (SCA) is characterized by immune system activation and heightened susceptibility to infections. We hypothesized that SCA patients exhibit transcriptional alterations in B-cell-related genes, impacting their peripheral B-cell compartment and leading to dysregulated humoral immunity and increased infection susceptibility. Our objective was to conduct an in silico analysis of whole blood transcriptomes from SCA patients and healthy controls obtained from public repositories.

Engineering NK-CAR.19 cells with the IL-15/IL-15Rα complex improved proliferation and anti-tumor effect .

Introduction: Natural killer 92 (NK-92) cells are an attractive therapeutic approach as alternative chimeric antigen receptor (CAR) carriers, different from T cells, once they can be used in the allogeneic setting. The modest outcomes observed with NK-92 cells continue to present hurdles in successfully translating NK-92 cell therapies into clinical applications. Adoptive transfer of CAR-NK-92 cells holds out the promise of therapeutic benefit at a lower rate of adverse events due to the absence of GvHD and cytokine release syndrome.

Engineering CAR-NK cells: how to tune innate killer cells for cancer immunotherapy.

Cell therapy is an innovative approach that permits numerous possibilities in the field of cancer treatment. CAR-T cells have been successfully used in patients with hematologic relapsed/refractory. However, the need for autologous sources for T cells is still a major drawback.

Allogeneic haematopoietic stem cell transplantation resets T- and B-cell compartments in sickle cell disease patients.

Objectives: Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). Here, we comprehensively evaluated the reconstitution of T- and B-cell compartments in 29 SCD patients treated with allo-HSCT and how it correlated with the development of acute graft-versus-host disease (aGvHD).

Methods: T-cell neogenesis was assessed by quantification of signal-joint and β-chain TCR excision circles.

Long-Term Effects of Allogeneic Hematopoietic Stem Cell Transplantation on Systemic Inflammation in Sickle Cell Disease Patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only currently available curative treatment for sickle cell disease (SCD). However, the effects of HSCT on SCD pathophysiology are poorly elucidated. Here, we assessed red blood cell (RBC) adhesiveness, intensity of hemolysis, vascular tone markers and systemic inflammation, in SCD patients treated with allogeneic HSCT.

Immune mechanisms involved in sickle cell disease pathogenesis: current knowledge and perspectives.

Sickle cell disease (SCD) is caused by a single point mutation in the β-chain of the hemoglobin gene that results in the replacement of glutamic acid with valine in the hemoglobin protein. However, recent studies have demonstrated that alterations in several other genes, especially immune related genes, may be associated with complications of SCD. In fact, higher chronic inflammatory status is related to more severe clinical symptoms in SCD patients, suggesting crucial roles of the immune system in SCD physiopathology.

Immunophenotypic Analysis of CAR-T Cells.

CAR-T cell immunotherapy is a promising therapeutic modality for cancer patients. The success of CAR-T cell therapy has been associated with the phenotype, activation and functional profiling of infused CAR-T cells. Therefore, immunophenotypic characterization of CAR-T cells during bioprocess is crucial for cell quality control and ultimately for improved antitumor efficacy.

Establishment of a simple and efficient platform for car-t cell generation and expansion: from lentiviral production to in vivo studies.

Introduction: Adoptive transfer of T cells expressing a CD19-specific chimeric antigen receptor (CAR) has shown impressive response rates for the treatment of CD19 + B-cell malignancies in numerous clinical trials. The CAR molecule, which recognizes cell-surface tumor-associated antigen independently of human leukocyte antigen (HLA), is composed by one or more signaling molecules to activate genetically modified T cells for killing, proliferation, and cytokine production.

Objectives: In order to make this treatment available for a larger number of patients, we developed a simple and efficient platform to generate and expand CAR-T cells.

Autologous Hematopoietic Stem Cell Transplantation for Autoimmune Diseases: From Mechanistic Insights to Biomarkers.

Phase I/II clinical trials of autologous hematopoietic stem cell transplantation (AHSCT) have led to increased safety and efficacy of this therapy for severe and refractory autoimmune diseases (AD). Recent phase III randomized studies have demonstrated that AHSCT induces long-term disease remission in most patients without any further immunosuppression, with superior efficacy when compared to conventional treatments. Immune monitoring studies have revealed the regeneration of a self-tolerant T and B cell repertoire, enhancement of immune regulatory mechanisms, and changes toward an anti-inflammatory milieu in patients that are responsive to AHSCT.