Clinical trial of umbilical cord blood NK cell transfusion combined with PD-1 inhibitor for treatment of multiple solid tumors
Ontology highlight
ABSTRACT:
DISEASE(S): Intermediate And Advanced Malignant Solid Tumors (including Colorectal Cancer, Lung Cancer, Esophageal Cancer, Stomach Cancer, Liver Cancer, Kidney Cancer And Malignant Melanoma)
PROVIDER: 2690767 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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2010-03-09 | E-GEOD-19293 | biostudies-arrayexpress
Project description:An evaluation of biopsies from patients with in-transit extremity melanoma who have been treated with melphalan in the setting of isolated limb infusion or isolated limb perfusion. Gene expression profiles were obtained from 21 lesions across 19 patients and evaluated for expression that correlated with response to melphalan isolated limb infusion. Chemotherapy response analysis: complete response - CR; partial response - PR; stable disease - SD; progressive disease - PD; not evaluable - n.e.
2011-12-22 | E-GEOD-34599 | biostudies-arrayexpress
Project description:ObjectiveInterest continues to grow regarding the therapeutic potential for umbilical cord blood therapies to modulate autoimmune disease. We conducted an open-label phase I study using autologous umbilical cord blood infusion to ameliorate type 1 diabetes.Research design and methodsFifteen patients diagnosed with type 1 diabetes and for whom autologous umbilical cord blood was stored underwent a single intravenous infusion of autologous cells and completed 1 year of postinfusion follow-up. Intensive insulin regimens were used to optimize glycemic control. Metabolic and immunologic assessments were performed before infusion and at established time periods thereafter.ResultsMedian (interquartile range [IQR]) age at infusion was 5.25 (3.1-7.3) years, with a median postdiagnosis time to infusion of 17.7 (10.9-26.5) weeks. No infusion-related adverse events were observed. Metabolic indexes 1 year postinfusion were peak C-peptide median 0.50 ng/ml (IQR 0.26-1.30), P = 0.002; A1C 7.0% (IQR 6.5-7.7), P = 0.97; and insulin dose 0.67 units * kg(-1) * day(-1) (IQR 0.55-0.77), P = 0.009. One year postinfusion, no changes were observed in autoantibody titers, regulatory T-cell numbers, CD4-to-CD8 ratio, or other T-cell phenotypes.ConclusionsAutologous umbilical cord blood transfusion in children with type 1 diabetes is safe but has yet to demonstrate efficacy in preserving C-peptide. Larger randomized studies as well as 2-year postinfusion follow-up of this cohort are needed to determine whether autologous cord blood-based approaches can be used to slow the decline of endogenous insulin production in children with type 1 diabetes.
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Project description:FcRγ-deficient natural killer (NK) cells, designated as g-NK cells, exhibit enhanced antibody-dependent cellular cytotoxicity (ADCC) capacity and increased IFN-γ and TNF-α production, rendering them promising for antiviral and antitumor responses. g-NK cells from peripheral blood (PB) are often associated with prior human cytomegalovirus (HCMV) infection. However, the prevalence, phenotype, and function of g-NK cells in umbilical cord blood (UCB-g-NK) remain unclear. Here, we demonstrate significant phenotypical differences between UCB-g-NK and PB-g-NK cells. Unlike PB-g-NK cells, UCB-g-NK cells did not show heightened cytokine production upon CD16 engagement, in contrast to the conventional NK (c-NK) cell counterparts. Interestingly, following in vitro activation, UCB-g-NK cells also exhibited elevated levels of IFN-γ production, particularly when co-cultured with HCMV and plasma from g-NK+ adults. Furthermore, g-NK+ plasma from PB even facilitated the in vitro expansion of UCB-g-NK cells. These findings underscore the phenotypic and functional heterogeneity of g-NK cells based on their origin and demonstrate that components within g-NK+ plasma may directly contribute to the acquisition of an adult phenotype by the "immature" UCB-g-NK cells.
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2011-01-01 | E-GEOD-22968 | biostudies-arrayexpress
Project description:We report the first application of human umbilical cord mesenchymal stem cell (HUCMSC)-derived therapy for pulmonary arterial hypertension (PAH). A 3-year-old female presented with heritable PAH (ACVLR1 missense mutation) associated with hereditary hemorrhagic telangiectasia (HHT). Serial intra-pulmonary arterial and centrally intravenous infusions of conditioned media (CM) from allogenic HUCMSCs resulted in marked clinical and hemodynamic improvement after six months. A consecutive multiple cord single-cell RNA-seq integrated analysis (HUCMSC and HUVEC control) revealed eight common cell clusters, of which two (overrepresented by HUCMSCs) had regenerative potential.
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Project description:In this study we evaluated the potential of expanded NK cells (eNKs) from two sources combined with the mAbs daratumumab and pembrolizumab to target primary multiple myeloma (MM) cells ex vivo. In order to ascertain the best source of NK cells, we expanded and activated NK cells from peripheral blood (PB) of healthy adult donors and from umbilical cord blood (UCB). The resulting expanded NK (eNK) cells express CD16, necessary for carrying out antibody-dependent cellular cytotoxicity (ADCC). Cytotoxicity assays were performed on bone marrow aspirates of 18 MM patients and 4 patients with monoclonal gammopathy of undetermined significance (MGUS). Expression levels of PD-1 on eNKs and PD-L1 on MM and MGUS cells were also quantified. Results indicate that most eNKs obtained using our expansion protocol express a low percentage of PD-1+ cells. UCB eNKs were highly cytotoxic against MM cells and addition of daratumumab or pembrolizumab did not further increase their cytotoxicity. PB eNKs, while effective against MM cells, were significantly more cytotoxic when combined with daratumumab. In a minority of cases, eNK cells showed a detectable population of PD1+ cells. This correlated with low cytotoxic activity, particularly in UCB eNKs. Addition of pembrolizumab did not restore their activity. Results indicate that UCB eNKs are to be preferentially used against MM in the absence of daratumumab while PB eNKs have significant cytotoxic advantage when combined with this mAb.
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Project description:We conducted an open-label, phase I study using autologous umbilical cord blood (UCB) infusion to ameliorate type 1 diabetes (T1D). Having previously reported on the first 15 patients reaching 1 year of follow-up, herein we report on the complete cohort after 2 years of follow-up.A total of 24 T1D patients (median age 5.1 years) received a single intravenous infusion of autologous UCB cells and underwent metabolic and immunologic assessments.No infusion-related adverse events were observed. ?-Cell function declined after UCB infusion. Area under the curve C-peptide was 24.3% of baseline 1 year postinfusion (P < 0.001) and 2% of baseline 2 years after infusion (P < 0.001). Flow cytometry revealed increased regulatory T cells (Tregs) (P = 0.04) and naive Tregs (P = 0.001) 6 and 9 months after infusion, respectively.Autologous UCB infusion in children with T1D is safe and induces changes in Treg frequency but fails to preserve C-peptide.
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Project description:We examined the safety and efficacy of human umbilical cord mesenchymal stem cell (hUC-MSC) infusion for immune non-responder (INR) patients with chronic HIV-1 infection, who represent an unmet medical need even in the era of efficient antiretroviral therapy (ART). Seventy-two INR patients with HIV were enrolled in this phase II randomized, double-blinded, multicenter, placebo-controlled, dose-determination trial (NCT01213186) from May 2013 to March 2016. They were assigned to receive high-dose (1.5 × 106/kg body weight) or low-dose (0.5 × 106/kg body weight) hUC-MSC, or placebo. Their clinical and immunological parameters were monitored during the 96-week follow-up study. We found that hUC-MSC treatment was safe and well-tolerated. Compared with baseline, there was a statistical increase in CD4+ T counts in the high-dose (P < 0.001) and low-dose (P < 0.001) groups after 48-week treatment, but no change was observed in the control group. Kaplan-Meier analysis revealed a higher cumulative probability of achieving an immunological response in the low-dose group compared with the control group (95.8% vs. 70.8%, P = 0.004). However, no significant changes in CD4/CD8+ T counts and CD4/CD8 ratios were observed among the three groups. In summary, hUC-MSC treatment is safe. However, the therapeutic efficacy of hUC-MSC treatment to improve the immune reconstitution in INR patients still needs to be further investigated in a large cohort study.
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