Development of a Novel CAR-T Therapy Targeting Translational Dysfunction in Exhausted T Cells

Development of a Novel CAR-T Therapy Targeting Translational Dysfunction in Exhausted T Cells - Development of a Novel CAR-T Therapy Targeting Translational Dysfunction in Exhausted T Cells

Status

Active, not recruiting

Phases

Unknown

Study type

Observational

Source

JPRN

Registry ID

JPRN-UMIN000059424

Enrollment

Registered

2025-10-25

Start date

2025-10-28

Completion date

Unknown

Last updated

2026-06-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Cancer

Interventions

None listed

Eligibility

Sex/Gender

All

Inclusion criteria

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.

Exclusion criteria

Exclusion criteria: [Lung Cancer Cases] Patients with malignant diseases other than lung cancer. [Healthy Volunteers] Individuals who are pregnant.

Design outcomes

Primary

Measure	Time frame
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.	—

Measure

Time frame

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.

—

Countries

Japan

Contacts

Public ContactRisa Shibuya

Tohoku University Department of Medical Science and Innovation, SiRIUS Institute of Medical Research

risa.shibuya.d3@tohoku.ac.jp0227178539

Outcome results