Nicotinamide enhances natural killer cell function and yields remissions in patients with non-Hodgkin lymphoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA920515 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23010337_1.fastq.gz | Fastqsanger.gz | |||
| SRR23010337_2.fastq.gz | Fastqsanger.gz | |||
| SRR23010338_1.fastq.gz | Fastqsanger.gz | |||
| SRR23010338_2.fastq.gz | Fastqsanger.gz | |||
| SRR23010339_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Natural killer (NK) cells are innate cytotoxic lymphocytes that play an important role in surveillance and elimination of cancer. Allogeneic NK cell adoptive transfer has shown the potential to induce remissions in relapsed/refractory acute myeloid leukemia (AML) and lymphomas, but strategies to enhance NK cell survival and function are needed to improve clinical efficacy. Here, preclinical data is presented demonstrating that NK cells cultured ex vivo with IL-15 and nicotinamide (NAM) exhibited significant and stable induction of CD62L, a lymphocyte adhesion molecule important for lymph node homing. High frequencies of CD62L were associated with elevated levels of the transcription factor forkhead box O1 (FOXO1), and NAM promoted the stability of FOXO1 by preventing ubiquitin-mediated proteasomal degradation. NK cells cultured with NAM exhibited metabolic changes associated with elevated glucose flux through the tricarboxylic acid cycle and protection against oxidative stress. Importantly, NK cells incubated with NAM displayed enhanced cytotoxicity and inflammatory cytokine production in vitro and were maintained at high levels xenogeneic adoptive transfer experiments. We report results from a first-in-human phase 1 clinical trial testing adoptive transfer of NK cells expanded ex vivo with IL-15 and NAM (GDA-201) combined with monoclonal antibodies in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and myeloma (NCT03019666). Cellular therapy with GDA-201 and rituximab was well-tolerated and yielded an overall response rate of 74% in 19 patients with advanced NHL. Thirteen patients had a complete response, and 1 patient had a partial response. GDA-201 cells were detected for up to 14 days in blood, bone marrow, and tumor tissues and maintained a favorable metabolic profile. The safety and efficacy of GDA-201 justify further development as a cancer therapy.
2023-01-13 | GSE222369 | GEO
Project description:Allogeneic natural killer (NK) cell adoptive transfer has shown the potential to induce remissions in relapsed or refractory leukemias and lymphomas, but strategies to enhance NK cell survival and function are needed to improve clinical efficacy. Here, we demonstrated that NK cells cultured ex vivo with interleukin-15 (IL-15) and nicotinamide (NAM) exhibited stable induction of l-selectin (CD62L), a lymphocyte adhesion molecule important for lymph node homing. High frequencies of CD62L were associated with elevated transcription factor forkhead box O1 (FOXO1), and NAM promoted the stability of FOXO1 by preventing proteasomal degradation. NK cells cultured with NAM exhibited metabolic changes associated with elevated glucose flux and protection against oxidative stress. NK cells incubated with NAM also displayed enhanced cytotoxicity and inflammatory cytokine production and preferentially persisted in xenogeneic adoptive transfer experiments. We also conducted a first-in-human phase 1 clinical trial testing adoptive transfer of NK cells expanded ex vivo with IL-15 and NAM (GDA-201) combined with monoclonal antibodies in patients with relapsed or refractory non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) (NCT03019666). Cellular therapy with GDA-201 and rituximab was well tolerated and yielded an overall response rate of 74% in 19 patients with advanced NHL. Thirteen patients had a complete response, and 1 patient had a partial response. GDA-201 cells were detected for up to 14 days in blood, bone marrow, and tumor tissues and maintained a favorable metabolic profile. The safety and efficacy of GDA-201 in this study support further development as a cancer therapy.
| S-EPMC10859734 | biostudies-literature
Project description:We report a novel phase 2 clinical trial in patients with poor prognosis refractory non-Hodgkin lymphoma (NHL) testing the efficacy of haploidentical donor natural killer (NK) cell therapy (NK dose 0.5-3.27?×?107 NK cells/kg) with rituximab and IL-2 (clinicaltrials.gov NCT01181258). Therapy was tolerated without graft-versus-host disease, cytokine release syndrome, or neurotoxicity. Of 14 evaluable patients, 4 had objective responses (29%; 95% CI 12-55%) at 2 months: 2 had complete response lasting 3 and 9 months. Circulating donor NK cells persisted for at least 7 days after infusion at the level 0.6-16 donor NK cells/µl or 0.35-90% of total CD56 cells. Responding patients had lower levels of circulating host-derived Tregs (17?±?4 vs. 307?±?152 cells/µL; p?=?0.008) and myeloid-derived suppressor cells at baseline (6.6 ± 1.4% vs. 13.0 ± 2.7%; p?=?0.06) than non-responding patients. Lower circulating Tregs correlated with low serum levels of IL-10 (R 2?=?0.64; p?<?0.003; n?=?11), suggestive of less immunosuppressive milieu. Low expression of PD-1 on recipient T cells before therapy was associated with response. Endogenous IL-15 levels were higher in responders than non-responding patients at the day of NK cell infusion (mean?±?SEM: 30?±?4; n?=?4 vs. 19.0?±?4.0 pg/ml; n?=?8; p?=?0.02) and correlated with day 14 NK cytotoxicity as measured by expression of CD107a (R 2?=?0.74; p?=?0.0009; n?=?12). In summary, our observations support development of donor NK cellular therapies for advanced NHL as a strategy to overcome chemoresistance. Therapeutic efficacy may be further improved through disruption of the immunosuppressive environment and infusion of exogenous IL-15.
| S-EPMC6055922 | biostudies-literature
Project description:Genomewide gene expression analysis of lymphoid cell lines of Hodgkin, non-Hodgkin and acute leukemia origin
2010-11-17 | GSE20011 | GEO
Project description:Genomewide gene expression analysis of lymphoid cell lines of Hodgkin, non-Hodgkin and acute leukemia origin Affymetrix U133 Plus 2.0 oligonucleotide arrays were hybridized to determine the gene expression profile of Hodgkin (L428, L1236, KM-H2, HDLM-2, L540, L540Cy), non-Hodgkin (Namalwa, SU-DHL-4) and acute lymphoblastic leukemia (Reh) cell lines; all hybridizations were done in biological duplicates (except L540, L50Cy, SU-DHL-4).
2010-11-17 | E-GEOD-20011 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE25986: Gene expression profiling of cell lines derived from classical Hodgkin lymphoma GSE25987: Gene expression profiling of Hodgkin lymphoma cell line KMH2: Comparison of CIITA-BX648577 knockdown cultures with non-silencing controls GSE25989: Copy number analysis of Hodgkin lymphoma cell lines KM-H2 and L-428 Refer to individual Series *** This submission represents the microarray gene expression and microarray copy number components of the study
2010-12-11 | E-GEOD-25990 | biostudies-arrayexpress
Project description:Culture of hematopoietic stem and progenitor cells in the presence of thrombopoietin induces megakaryocytic differentiation. Addition of nicotinamide to thrombopoietin-stimulated cultures results in significant increases in megkaryocytic differentiation including greater polyploidization and enhanced proplatelet formation. This study focuses on understanding the differences in the temporal gene expression pattern during differentiation with and without nicotinamide. Nicotinamide was added on day 5. Experiment Overall Design: Two biological experiments were analyzed. For each experiment, a sample was taken on day 5, before nicotinamide addition, and on days 6, 8, and 10 from both nicotinamide and control treated cultures. Each sample was analyzed in duplicate for a total of 14 hybridizations per culture or 28 total hybridizations.
2009-04-08 | E-GEOD-4974 | biostudies-arrayexpress
Project description:To investigate the efficacy of nicotinamide treatment using our ex-vivo primary lymphocyte model, we performed high-throughput RNA sequencing on libraries generated from untreated and nicotinamide treated samples. PBMC isolated from FRDA affected individuals were cultured to prepare the primary lymphocyte cell lines. The primary cultured cells were either treated with 10mM nicotinamide or without the addition of drug during the 3-days treatment. RNA was extracted after the treatment and then RNA-seq libraries were generated by standard protocols.
2013-04-03 | E-GEOD-42960 | biostudies-arrayexpress
Project description:Culture of hematopoietic stem and progenitor cells in the presence of thrombopoietin induces megakaryocytic differentiation. Addition of nicotinamide to thrombopoietin-stimulated cultures results in significant increases in megkaryocytic differentiation including greater polyploidization and enhanced proplatelet formation. This study focuses on understanding the differences in the temporal gene expression pattern during differentiation with and without nicotinamide. Nicotinamide was added on day 5. Keywords: treatment response
2006-08-25 | GSE4974 | GEO
Project description:Nicotinamide, the amide form of vitamin B3, is essential to maintain the human fetal development. It benefits the ectoderm and endoderm development, but its influence in mesoderm differentiation is elusive. In this study, we reported that nicotinamide regulated the gene expression of cardiovascular system, and it induced functional cardiomyocytes which was independent of canonical WNT signaling. Through a kinase screening, we found that nicotinamide inhibited the activity of P38δ to promote cardiomyocyte differentiation. Furthermore, we compared the gene expression of cardiomyocytes induced by WNT inhibitor IWP-2, nicotinamide or P38 inhibitor SB202190. The results showed that the cardiomyocytes induced by nicotinamide had similar gene expression profile compared with P38 inhibitor, which indicated nicotinamide promoted cardiac differentiation via the inhibition of P38.
2021-12-01 | GSE154454 | GEO