Clinical trial · Observational
Study on the Mechanism of ADC Drug Evaluation Based on Immune Co-culture of Lung Cancer Organoids
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
A case-control study was conducted to evaluate the efficacy and mechanism of action of antibody-drug conjugates (ADCs) in lung cancer, utilizing patient-derived organoid (PDO)-immune co-cultures. Focusing on HER2-positive and TROP2-positive non-small cell lung cancer (NSCLC) cases, ADC candidates were screened for in vitro activity based on organoid-immune interaction models. Key assessments included: Tumor killing efficiency, assessed by dose-response relationships; Drug internalization (cellular uptake), as a measure of penetration into cancer cells; Antibody-dependent cellular cytotoxicity (ADCC) and bystander effect, with negative control targets employed to delineate specificity; Single-cell RNA sequencing, to profile transcriptional alterations at single-cell resolution. Data demonstrated distinct ADC responses correlating with target expression and immune microenvironment features. The integrated approach provided cell-based evidence of ADC potency and revealed mechanistic insights-including immune-mediated cytotoxicity pathways and intracellular trafficking-supporting the rational design of clinical trials. These findings established a foundation for precision immunotherapy strategies and offered a mechanistic rationale for patient selection in HER2/TROP2-positive lung cancer.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| HER2 Positive OR TROP2 Positive Non-Small Cell Lung Cancer | Lung Non-Small Cell Carcinoma | ALIAS | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Antibody-drug conjugate (ADC) combination therapy | Drug | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- label
- HER2 Positive OrTROP2 Positive non-small cell lung cancer
- description
- The abundance of HER2 or TROP2 target expression was determined by immunohistochemistry and categorized into strongly positive and weakly positive groups, representing the experimental group and negative control group, respectively. Using an immunococulture system based on patient-derived organoids, the in vitro activity of antibody-drug conjugates (ADCs)-including trastuzumab emtansine (an approved ADC administered intravenously)-that are either approved or currently in clinical trials was evaluated. In parallel, clinical patients provided ex vivo cytological assay results indicating their sensitivity to ADC therapy.
- interventionNames
- Drug: Antibody-drug conjugate (ADC) combination therapy
Primary outcomes (4)
- measure
- Changes in ATP assay of tumor patient-derived organoids (PDOs) under treatment with ADCs and various drug combinations
- timeFrame
- Tumor viability assessed by luminescence measurement at 72 hours after co-culture with immune cells
- description
- The single high-concentration ADC design was formulated to mimic the peak plasma concentration achieved after clinical administration, thereby directly reflecting the cytotoxic potency of the drug at effective concentrations. The combination therapy assessment focuses on the current trend of "ADC + immuno" strategies in oncology, providing ex vivo data to support optimization of clinical dosing regimens.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 100 Years
Show eligibility criteria text
Inclusion Criteria: * Age ≥ 18 years. * Availability of patient-derived organoids (PDOs) with matched autologous tumor-infiltrating lymphocytes (TILs) or peripheral blood mononuclear cells (PBMCs) from non-small cell lung cancer (NSCLC) cases. * Patients currently undergoing or scheduled to receive Trastuzumab deruxtecan (T-DXd) therapy who meet clinical eligibility criteria. * Provision of written informed consent. * PDOs exhibiting strong positive HER2 and TROP2 expression by immunohistochemistry (IHC) assigned to the experimental group. * PDOs exhibiting weak positive HER2 and TROP2 expression by IHC assigned to the negative control group. Exclusion Criteria: * PDOs derived from patients with pathologically confirmed small cell lung cancer (SCLC). * Unavailability of matched autologous PDOs, TILs, or PBMCs. * Presence of any contraindications to T-DXd treatment. * Presence of other serious comorbidities resulting in an estimated survival of \<3 months. * Pregnant or breastfeeding women.
References
Publications (4)
- RESULTEltayeb E. Nance, Michael J. D. Gooden, Francesca M. Marcon; Antibody Fragments as Agonists and Antagonists in Cancer Therapy; Antibodies; 2023 Apr; 12; 72.
- RESULTHammood M, Craig AW, Leyton JV. Impact of Endocytosis Mechanisms for the Receptors Targeted by the Currently Approved Antibody-Drug Conjugates (ADCs)-A Necessity for Future ADC Research and Development. Pharmaceuticals (Basel). 2021 Jul 15;14(7):674. doi: 10.3390/ph14070674. PMID 34358100
- RESULTFu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the "biological missile" for targeted cancer therapy. Signal Transduct Target Ther. 2022 Mar 22;7(1):93. doi: 10.1038/s41392-022-00947-7. PMID 35318309
- RESULTBirrer MJ, Moore KN, Betella I, Bates RC. Antibody-Drug Conjugate-Based Therapeutics: State of the Science. J Natl Cancer Inst. 2019 Jun 1;111(6):538-549. doi: 10.1093/jnci/djz035. PMID 30859213