UMIN-CTR Clinical Trial
| Unique ID issued by UMIN | UMIN000059424 |
|---|---|
| Receipt number | R000067901 |
| Scientific Title | Development of a Novel CAR-T Therapy Targeting Translational Dysfunction in Exhausted T Cells |
| Date of disclosure of the study information | 2025/10/25 |
| Last modified on | 2025/10/25 14:06:27 |
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Basic information
Public title
Development of a Novel CAR-T Therapy Targeting Translational Dysfunction in Exhausted T Cells
Acronym
Development of a Novel CAR-T Therapy Targeting Translational Dysfunction in Exhausted T Cells
Scientific Title
Development of a Novel CAR-T Therapy Targeting Translational Dysfunction in Exhausted T Cells
Scientific Title:Acronym
Development of a Novel CAR-T Therapy Targeting Translational Dysfunction in Exhausted T Cells
Region
| Japan |
Condition
Condition
Lung Cancer
Classification by specialty
| Pneumology |
Classification by malignancy
Malignancy
Genomic information
NO
Objectives
Narrative objectives1
The aim of this study is to develop a novel CAR-T cell therapy that restores the antitumor activity of T cells through the regulation of protein translation, with a particular focus on tRNA modifications and ribosomal function.
Basic objectives2
Others
Basic objectives -Others
To elucidate the relationship between translational control, particularly tRNA modifications, and T-cell antitumor activity, and to explore novel translational mechanisms that can be applied to the development of next-generation CAR-T therapies.
Trial characteristics_1
Trial characteristics_2
Developmental phase
Assessment
Primary outcomes
In this study, to evaluate the relationship between the status of tRNA modifications or translational regulation and the clinical characteristics and therapeutic responses of tumors in patients with non-small cell lung cancer (NSCLC), the following tumor evaluation parameters will be used.
As clinical evaluation parameters, treatment responses to immune checkpoint inhibitors (ICIs) and combined chemoimmunotherapy (Chemo + ICI) will be classified as partial response (PR), stable disease (SD), or progressive disease (PD) according to the RECIST guidelines, and correlated with the expression levels of translation-related factors.
Additional clinical variables, including tumor stage (TNM classification), histological type, driver gene alterations (e.g., EGFR, ALK), and prior immunotherapy history, will also be collected and used for stratified analyses.
Furthermore, to support survival analyses, overall survival (OS) and progression-free survival (PFS) will be followed. Statistical evaluations will be performed to assess the associations between these clinical parameters and tRNA modification profiles or translational stress response markers, aiming to elucidate how translational mechanisms influence immune response and treatment sensitivity.
In in vitro experiments, the following parameters will be assessed: cytotoxic activity of CAR-T cells, cytokine production (IFN-gamma, TNF-alpha, IL-2, etc.), translational stress response markers, and T-cell exhaustion markers (PD-1, TIM-3, LAG-3). Functional changes in CAR-T cells under manipulated translational conditions will be quantitatively analyzed.
Key secondary outcomes
Base
Study type
Observational
Study design
Basic design
Randomization
Randomization unit
Blinding
Control
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment
Intervention
No. of arms
Purpose of intervention
Type of intervention
Interventions/Control_1
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10
Eligibility
Age-lower limit
| 20 | years-old | <= |
Age-upper limit
| Not applicable |
Gender
Male and Female
Key inclusion criteria
Patients diagnosed with lung cancer based on histological or cytological examination.
No restriction on disease stage.
Age >= 20 years at the time of presentation to our institution.
No restriction on sex.
Patients who have provided informed consent for sample storage and research use through either:
the Department of Respiratory Medicine Biobank (Project title: Establishment of a biobank system for the preservation and management of biospecimens obtained from surgical, bronchoscopic, and fluid drainage samples for respiratory diseases), or the Tohoku University Hospital Biobank (Project title: Tohoku University Hospital Personalized Medicine Center Biobank Division).
[Healthy Volunteers]
Age >= 20 years at the time of participation.
No restriction on sex.
No ongoing treatment for malignant or autoimmune diseases.
Voluntarily provided written informed consent for participation in this study.
Key exclusion criteria
[Lung Cancer Cases]
Patients with malignant diseases other than lung cancer.
[Healthy Volunteers]
Individuals who are pregnant.
Target sample size
50
Research contact person
Name of lead principal investigator
| 1st name | Risa |
| Middle name | |
| Last name | Shibuya |
Organization
Tohoku University
Division name
Department of Medical Science and Innovation, SiRIUS Institute of Medical Research
Zip code
980-8574
Address
1-1 Seiryomachi, Aoba Ward, Sendai, Miyagi
TEL
0227178539
risa.shibuya.d3@tohoku.ac.jp
Public contact
Name of contact person
| 1st name | Risa |
| Middle name | |
| Last name | Shibuya |
Organization
Tohoku University
Division name
Department of Medical Science and Innovation, SiRIUS Institute of Medical Research
Zip code
980-8574
Address
1-1 Seiryomachi, Aoba Ward, Sendai, Miyagi
TEL
0227178539
Homepage URL
risa.shibuya.d3@tohoku.ac.jp
Sponsor or person
Institute
Tohoku University
Institute
Department
Personal name
Funding Source
Organization
Ministry of Education, Culture, Sports, Science and Technology (MEXT)
Organization
Division
Category of Funding Organization
Japanese Governmental office
Nationality of Funding Organization
Other related organizations
Co-sponsor
Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine
Name of secondary funder(s)
IRB Contact (For public release)
Organization
Tohoku University Hospital Clinical Research Ethics Committee Clinical Research Ethics Committee, Tohoku University Hospital
Address
1-1 Seiryomachi, Aoba Ward, Sendai, Miyagi
Tel
022-728-4105
1-1 Seiryomachi, Aoba Ward, Sendai, Miyagi
Secondary IDs
Secondary IDs
NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW
Institutions
Institutions
Other administrative information
Date of disclosure of the study information
| 2025 | Year | 10 | Month | 25 | Day |
Related information
URL releasing protocol
Publication of results
Unpublished
Result
URL related to results and publications
Number of participants that the trial has enrolled
Results
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description
Progress
Recruitment status
Preinitiation
Date of protocol fixation
| 2025 | Year | 08 | Month | 08 | Day |
Date of IRB
| 2025 | Year | 10 | Month | 28 | Day |
Anticipated trial start date
| 2025 | Year | 10 | Month | 28 | Day |
Last follow-up date
| 2030 | Year | 09 | Month | 30 | Day |
Date of closure to data entry
Date trial data considered complete
Date analysis concluded
Other
Other related information
[Subjects]
Healthy volunteers aged 20 years or older will be included, regardless of sex. Individuals with active malignant or autoimmune diseases or those who are pregnant will be excluded.
[Observation Content]
Peripheral blood samples (20-50 mL) will be collected once from each participant. T cells will be isolated from the samples to generate CAR-T cells, followed by molecular analyses of translation control, tRNA modifications, and amino acid metabolism-related factors. These analyses aim to elucidate the translational mechanisms in healthy T cells and obtain comparative data against exhausted T cells observed in cancer immunotherapy.
[Observation Method]
Blood collection will be performed by a physician or a certified medical technologist under sterile conditions. After collection, T cells will be isolated, and analyses such as RNA extraction, LC-MS, and gene expression profiling will be conducted using molecular biology techniques. All analyses will be performed using anonymized sample IDs to ensure that individuals cannot be identified.
[Analysis and Evaluation Items]
The primary evaluation item is the alteration of translation control and tRNA modification profiles observed in exhausted CAR-T cells.
Management information
Registered date
| 2025 | Year | 10 | Month | 16 | Day |
Last modified on
| 2025 | Year | 10 | Month | 25 | Day |
Link to view the page
Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000067901
