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Allogeneic Vγ9Vδ2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis.

ABSTRACT: The WHO's "Global tuberculosis report 2020" lists tuberculosis (TB) as one of the leading causes of death globally. Existing anti-TB therapy strategies are far from adequate to meet the End TB Strategy goals set for 2035. Therefore, novel anti-TB therapy protocols are urgently needed. Here, we proposed an allogeneic Vγ9Vδ2 T-cell-based immunotherapy strategy and clinically evaluated its safety and efficacy in patients with multidrug-resistant TB (MDR-TB). Eight patients with MDR-TB were recruited in this open-label, single-arm pilot clinical study. Seven of these patients received allogeneic Vγ9Vδ2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 × 10⁸) were infused per treatment every 2 weeks, with 12 courses of cell therapy conducted for each patient, who were then followed up for 6 months to evaluate the safety and efficacy of cell therapy. The eighth patient initially received four courses of cell infusions, followed by eight courses of cell therapy plus anti-MDR-TB drugs. Clinical examinations, including clinical response, routine blood tests and biochemical indicators, chest CT imaging, immune cell surface markers, body weight, and sputum Mycobacterium tuberculosis testing, were conducted. Our study revealed that allogeneic Vγ9Vδ2 T cells are clinically safe for TB therapy. These cells exhibited clinical efficacy in multiple aspects, including promoting the repair of pulmonary lesions, partially improving host immunity, and alleviating M. tuberculosis load in vivo, regardless of their application in the presence or absence of anti-TB drugs. This pilot study opens a new avenue for anti-TB treatment and exhibits allogeneic Vγ9Vδ2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy.

Clinical trial registration

(https://clinicaltrials.gov/ct2/results?cond=&term=NCT03575299&cntry=&state=&city=&dist=) ( NCT03575299).

SUBMITTER: Liang J

PROVIDER: S-EPMC8715986 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:PurposeBreast cancer-related lymphedema (BCRL) is a chronic, progressive side effect of breast cancer treatment, occurring in one-third of patients treated with axillary lymph node dissection and nodal radiotherapy. Cluster of differentiation 4-positive (CD4+) cells plays a key role in BCRL by facilitating inflammation and inhibiting lymphangiogenesis. Tacrolimus is an anti-inflammatory and immunosuppressive macrolide that targets CD4+ cells. Treatment of lymphedema with topical tacrolimus has revealed promising results in preclinical trials. This clinical trial was aimed at evaluating the feasibility, safety, and effect of tacrolimus in women with stage I or II BCRL, according to the International Society of Lymphology.MethodsWe conducted this open-label, single-arm, phase II pilot trial from September 2020 to April 2021. Eighteen women with BCRL stage I or II BCRL were treated with topical tacrolimus for 6 months and followed up at 3 and 6 months. The primary outcome was arm volume, and secondary outcomes were the lymphedema index (L-Dex), health-related quality of life (HRQoL), lymph flow and function, and safety and feasibility of the trial design.ResultsThe mean lymphedema arm volume and L-Dex reduced significantly by 130.44 ± 210.13 mL (p < 0.05; relative reduction: 3.6%) and 3.54 ± 4.98 (p < 0.05), respectively, and health-related quality of life scores was improved significantly (p < 0.05). According to the MD Anderson scale, in terms of lymph flow and function, three patients (16.7%) showed improvement, while none showed worsening. Lymph flow or function showed no change according to the Arm Dermal Backflow scale.ConclusionIn this trial, treatment with tacrolimus was safe and feasible in women with stage I or II BCRL. Tacrolimus alleviated BCRL in terms of improved arm volume, L-Dex, and HRQoL. Assessments of lymph flow and function were positive, although inconclusive. Larger randomized controlled trials are required to verify these findings.Trial registrationClinicalTrials.gov Identifier: NCT04541290.

Project description:AbstractGait automaticity is reduced in patients with Parkinson disease (PD) due to impaired habitual control. The aim of this study was to investigate the effect of robot-assisted gait training (RAGT) on gait automaticity as well as gait speed and balance in patients with PD.This study was a prospective, open-label, single-arm, pilot study. We planned to recruit 12 patients with idiopathic PD. Participants received 12 sessions of RAGT using exoskeleton-type robotic device. Sessions were 45-minute each, 3 days a week, for 4 consecutive weeks using an exoskeleton-type gait robot. The primary outcome was the percentage of dual-task interference measured by the 10-Meter Walk Test (10MWT) under single and dual-task (cognitive and physical) conditions. Secondary outcomes were the Berg Balance Scale and Korean version of the Falls Efficacy Scale-International. All measures were evaluated before treatment (T0), after treatment (T1), and 1-month post-treatment (T2).Twelve patients were enrolled and 1 dropped out. Finally, 11 patients with idiopathic PD were analyzed. The mean age of 11 patients (5 males) was 66.46 ± 5.66 years, and disease duration was 112.91 ± 50.19 months. The Hoehn and Yahr stages were 2.5 in 8 patients and 3 in 3 patients. Linear mixed-effect model analysis showed a significant change over time only in single-task gait speed of the 10MWT (P = .007), but not in dual-task gait speed, dual-task interferences, and Korean version of the Falls Efficacy Scale-International. Cognitive dual-task interference significantly increased (P = .026) at T1, but not at T2 (P = .203). No significant changes were observed for physical dual-task interference at T1 and T2. Single-task gait speed of the 10MWT was significantly increased at T1 (P = .041), but not at T2 (P = .445). There were no significant changes in the dual-task gait speed of 10MWT. A significant improvement was observed in Berg Balance Scale score at T1 and T2 (P = .004 and P = .024, respectively).In this pilot study, despite improvement in walking speed and balance, gait automaticity in patients with PD was not improved by RAGT using an exoskeleton-type robot. Additional therapeutic components may be needed to improve gait automaticity using RAGT in patients with PD.

Project description:BackgroundGraft-versus-host disease (GVHD), particularly acute digestive GVHD (aDGVHD), is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). It is necessary to identify predictive factors of GVHD to adapt prophylactic treatment.ObjectiveIn this context, our pilot study aimed (i) to determine whether an early remodeling of the colonic mucosa occurred after allo-HSCT and (ii) to identify potential predictive mucosal markers of aDGVHD after allo-HSCT.MethodsBetween day 21 and day 28 after the allo-HSCT, 19 allo-HSCT patients were included and had a rectosigmoidoscopy with probe-based confocal laser endomicroscopy (pCLE) recording and biopsies. Sixteen patients were included in the control group. Morphological (pCLE), functional (intestinal permeability), and inflammatory parameters (cytokine multiplex immunoassay) were assessed.ResultsAmong allo-HSCT patients, 11 patients developed GVHD, and 6 of them developed aDGVHD. Morphological and functional changes of the colonic mucosa occurred after allo-HSCT. Indeed, the perimeter of colonic crypts was significantly increased in allo-HSCT patients compared to controls as well as crypt lumen fluorescein leakage (53% vs. 9%), whereas crypts sphericity, roundness, Feret diameter, and mean vessel area were significantly decreased in allo-HSCT patients compared to the control group. In addition, interleukin-6 (IL-6), IL-33, and IL-15 levels in the supernatants of 24 h explant cultures of colonic biopsies were significantly increased in allo-HSCT patients compared to controls. Finally, there was no difference in pCLE parameters, intestinal permeability, and inflammatory cytokines between patients who developed aDGVHD and those who did not.ConclusionThis pilot study identified early colonic mucosa remodeling after allo-HSCT conditioning therapy, that is morphological and functional mucosal alterations as well as mucosal inflammation. As to whether these changes are first steps in GVHD initiation and could be considered as predictive biomarkers of aDGVHD need to be determined in a larger cohort of patients.

Dataset Information

Allogeneic Vγ9Vδ2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis.

Clinical trial registration

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