Similar Datasets
Project description:Second-generation CD19-targeted chimeric antigen receptors (CAR) have an antigen-binding domain fused to transmembrane, co-stimulatory, and CD3ζ domains. The two CARs with regulatory approval include a CD28 or 4-1BB co-stimulatory domain. While both CARs achieve similar clinical outcomes, biologic differences between the two endodomains have become apparent but not completely understood. The objective is to evaluate gene expression in different mouse CD19-targeted CAR T cells, including m19z, m1928z and m19-musBBz.
2018-07-31 | GSE111641 | GEO
Project description:Second-generation CD19-targeted chimeric antigen receptors (CAR) have an antigen-binding domain fused to transmembrane, co-stimulatory, and CD3ζ domains. The two CARs with regulatory approval include a CD28 or 4-1BB co-stimulatory domain. While both CARs achieve similar clinical outcomes, biologic differences between the two endodomains have become apparent but not completely understood. The objective is to evaluate gene expression in different mouse CD19-targeted CAR T cells, including m19z, m1928z and m19-humBBz.
2018-07-31 | GSE112566 | GEO
Project description:Expression data from mouse CD19-targeted CAR (chimeric antigen receptor) T cells after antigen stimulation
| PRJNA448188 | ENA
Project description:BackgroundAggressive B cell lymphoma with secondary central nervous system (CNS) involvement (SCNSL) carries a dismal prognosis. Chimeric antigen receptor (CAR) T cells (CAR-T) targeting CD19 have revolutionized the treatment for B cell lymphomas; however, only single cases with CNS manifestations successfully treated with CD19 CAR-T have been reported.MethodsWe prospectively enrolled 4 patients with SCNSL into our study to assess clinical responses and monitor T cell immunity.ResultsTwo of four SNCSL patients responded to the CD19-targeted CAR-T. Only one patient showed a substantial expansion of peripheral (PB) CAR-T cells with an almost 100-fold increase within the first week after CAR-T. The same patient also showed marked neurotoxicity and progression of the SNCSL despite continuous surface expression of CD19 on the lymphoma cells and an accumulation of CD4+ central memory-type CAR-T cells in the CNS. Our studies indicate that the local production of chemokine IP-10, possibly through its receptor CXCR3 expressed on our patient's CAR-T, could potentially have mediated the local accumulation of functionally suboptimal anti-tumor T cells.ConclusionsOur results demonstrate expansion and homing of CAR-T cells into the CNS in SNCSL patients. Local production of chemokines such as IP-10 may support CNS infiltration by CAR-T cells but also carry the potential of amplifying local toxicity. Future studies investigating numbers, phenotype, and function of CAR-T in the different body compartments of SNSCL patients receiving CAR-T will help to improve local delivery of "fit" and highly tumor-reactive CAR-T with low off-target reactivity into the CNS.
| S-EPMC10864416 | biostudies-literature
Project description:Expression data from mouse CD19-targeted CAR (chimeric antigen receptor) T cells after antigen stimulation [RNA-seq]
| PRJNA448192 | ENA
Project description:Expression data from mouse CD19-targeted CAR (chimeric antigen receptor) T cells after antigen stimulation [expression array]
| PRJNA437645 | ENA
Project description:Lymphodepletion chemotherapy with CD19-targeted chimeric antigen receptor-modified T (CAR-T)-cell immunotherapy is a novel treatment for refractory or relapsed B-cell malignancies. Infectious complications of this approach have not been systematically studied. We evaluated infections occurring between days 0 to 90 in 133 patients treated with CD19 CAR-T cells in a phase 1/2 study. We used Poisson and Cox regression to evaluate pre- and posttreatment risk factors for infection, respectively. The cohort included patients with acute lymphoblastic leukemia (ALL; n = 47), chronic lymphocytic leukemia (n = 24), and non-Hodgkin lymphoma (n = 62). There were 43 infections in 30 of 133 patients (23%) within 28 days after CAR-T-cell infusion with an infection density of 1.19 infections for every 100 days at risk. There was a lower infection density of 0.67 between days 29 and 90 (P = .02). The first infection occurred a median of 6 days after CAR-T-cell infusion. Six patients (5%) developed invasive fungal infections and 5 patients (4%) had life-threatening or fatal infections. Patients with ALL, ≥4 prior antitumor regimens, and receipt of the highest CAR-T-cell dose (2 × 107 cells per kg) had a higher infection density within 28 days in an adjusted model of baseline characteristics. Cytokine release syndrome (CRS) severity was the only factor after CAR-T-cell infusion associated with infection in a multivariable analysis. The incidence of infections was comparable to observations from clinical trials of salvage chemoimmunotherapies in similar patients. This trial was registered at www.clinicaltrials.gov as #NCT01865617.
| S-EPMC5755046 | biostudies-literature
Project description:Human T cells isolated from healthy donors were transduced with non-tonically signaling CARs or tonically signaling CARs, each with CD28z or 4-1BB costimulatory domains Human T cells isolated from healthy donors were transduced with non-tonically signaling CARs or tonically signaling CARs, each with CD28z or 4-1BB costimulatory domains
2015-04-09 | E-GEOD-65856 | biostudies-arrayexpress
Project description:CD19-targeted chimeric antigen receptor-modified T cell (CAR-T cell) therapy has shown excellent antitumor activity in patients with relapsed/refractory B cell malignancies, with very encouraging response rates and outcomes. However, the late effects following this therapy remain unknown. Here we report late adverse events-defined as starting or persisting beyond 90 days after CAR-T cell infusion-in patients who survived at least 1 year after therapy. The median duration of follow-up was 28.1 months (range, 12.5 to 62.6 months). At last follow-up, 73% of patients were still alive and 24% were in ongoing complete remission (CR). The most common late adverse event was hypogammaglobulinemia (IgG <400 mg/dL or i.v immunoglobulinm (IVIG) replacement, observed in 67% of the patients with available data. Infection density was .55 infection/100 days at risk (2.08 per patient-year). The majority (80%) of the infections were treated in the outpatient setting, and 5% necessitated admission to the intensive care unit (ICU). Subsequent malignancies occurred in 15% of patients, including 5% with myelodysplastic syndrome (MDS). Among patients with ongoing CR and with no MDS, 16% experienced prolonged cytopenia requiring transfusions or growth factor support. Graft-versus-host disease occurred in 3 of 15 patients (20%) who had undergone previous allogeneic hematopoietic cell transplantation. Most of the late events observed in this cohort were not severe, and many could be related to previous or subsequent therapies, suggesting a safe long-term profile of CD19-targeted CAR-T cell immunotherapy.
| S-EPMC6953906 | biostudies-literature
Project description:Clinical trials targeting CD19 on B-cell malignancies are underway with encouraging anti-tumor responses. Most infuse T cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of a CD19-specific mouse monoclonal antibody (mAb, clone FMC63). We describe a novel anti-idiotype monoclonal antibody (mAb) to detect CD19-specific CAR(+) T cells before and after their adoptive transfer. This mouse mAb was generated by immunizing with a cellular vaccine expressing the antigen-recognition domain of FMC63. The specificity of the mAb (clone no. 136.20.1) was confined to the scFv region of the CAR as validated by inhibiting CAR-dependent lysis of CD19(+) tumor targets. This clone can be used to detect CD19-specific CAR(+) T cells in peripheral blood mononuclear cells at a sensitivity of 1?1,000. In clinical settings the mAb is used to inform on the immunophenotype and persistence of administered CD19-specific T cells. Thus, our CD19-specific CAR mAb (clone no. 136.20.1) will be useful to investigators implementing CD19-specific CAR(+) T cells to treat B-lineage malignancies. The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy.
| S-EPMC3585808 | biostudies-literature