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    Ad-CCL21-DC

    i
    Other names: Ad-CCL21-DC, autologous dendritic cell-adenovirus CCL21 vaccine, DC-AdCCL21
    Associations

    News

    Trials
    Company:
    National Cancer Institute
    Drug class:
    Immunostimulant
    Related drugs:
    Associations

    News

    Trials
    1m
    Characteristics of a CCL21-gene modified dendritic cell vaccine utilized for a clinical trial in non-small cell lung cancer. (PubMed, Mol Cancer Ther)
    We have embarked on a phase I clinical trial of a vaccine consisting of monocyte-derived DCs (moDCs) modified to express the chemokine CCL21 (CCL21-DC) given in combination with pembrolizumab. A single freeze-thaw cycle for stored vaccines was associated with minor alterations to the DC phenotype, as was the use of healthy donors rather than patient autologous blood. Our results highlight important considerations for the production of DC vaccines and identify underexplored factors that may affect their efficacy and immunologic impact.
    Journal
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    CCL21 (C-C Motif Chemokine Ligand 21)
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    Keytruda (pembrolizumab) • Ad-CCL21-DC
    8ms
    HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=24, Active, not recruiting, Jonsson Comprehensive Cancer Center | Recruiting --> Active, not recruiting | Trial completion date: Jun 2025 --> Jan 2025 | Trial primary completion date: Jun 2024 --> Jan 2024
    Enrollment closed • Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1)
    |
    EGFR mutation • EGFR T790M • ALK rearrangement
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC
    1year
    CCL21-DC in situ vaccination in murine NSCLC overcomes resistance to immunotherapy and generates systemic tumor-specific immunity. (PubMed, J Immunother Cancer)
    CCL21-DC ISV synergizes with anti-PD-1 to eradicate murine NSCLC. Our data support the clinical application of CCL21-DC ISV in combination with checkpoint inhibition for patients with NSCLC.
    Preclinical • Journal • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • CCL21 (C-C Motif Chemokine Ligand 21)
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    TP53 mutation • KRAS mutation
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    Ad-CCL21-DC
    over1year
    HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=24, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jun 2024 --> Jun 2025 | Trial primary completion date: Jun 2023 --> Jun 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule) • CCL21 (C-C Motif Chemokine Ligand 21)
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    PD-L1 expression • EGFR mutation • EGFR T790M • ALK rearrangement • CD8 expression
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    Keytruda (pembrolizumab) • Ad-CCL21-DC
    over2years
    Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC (ESMO 2022)
    Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment.
    P1 data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • EGFR mutation • ALK positive • EGFR wild-type • ALK mutation • ALK wild-type • EGFR positive
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC
    over2years
    Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC. (ASCO 2022)
    Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial is currently open for enrollment.
    P1 data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • EGFR mutation • ALK rearrangement • EGFR wild-type • ALK mutation • ALK wild-type
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC
    almost3years
    In situ vaccination with CCL21-DC sensitizes non-responsive murine NSCLCs to anti-PD-1 therapy and generates systemic tumor-specific immune memory (AACR 2022)
    Combination therapy enhances anti-tumor T cell responses, resulting in immunoediting of tumor subclones and the generation of systemic tumor-specific immunity. In an ongoing clinical trial, we are evaluating the safety and efficacy of ISV with CCL21-DC in combination with anti-PD-1, pembrolizumab, in patients with advanced NSCLC who have progressed on front-line therapy.
    Preclinical • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • STK11 (Serine/threonine kinase 11) • CD8 (cluster of differentiation 8) • ITGAE (Integrin Subunit Alpha E)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • KRAS G12D • TMB-L • KRAS G12
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC
    almost3years
    Phase I trial of in situ vaccination with autologous CCL21 gene-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced non-small cell lung cancer (NSCLC) (AACR 2022)
    Secondary objectives include adverse event profiling and immune monitoring studies.[B.L. and A.L. contributed equally to this work as first authors.]
    P1 data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase)
    |
    EGFR mutation • EGFR wild-type • ALK mutation • ALK wild-type
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC
    over3years
    [VIRTUAL] Phase I Trial of in Situ Vaccination With Autologous CCL21 - Modified Dendritic Cells (CCL21 - DC) Combined With Pembrolizumab for Advanced NSCLC (IASLC-WCLC 2021)
    Our preclinical studies and phase I trial of intratumoral (IT) administration of DC genetically modified to overexpress CCL21 (CCL21-DC) revealed augmentation of tumor antigen presentation in situ, resulting in effective T cell responses and systemic antitumor immunity. Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies. This trial, NCT03546361, is currently open for enrollment.
    P1 data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • EGFR mutation • ALK rearrangement • ALK mutation
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC
    over3years
    HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=24, Recruiting, Jonsson Comprehensive Cancer Center | Trial completion date: Jun 2023 --> Jun 2024 | Trial primary completion date: Jun 2022 --> Jun 2023
    Clinical • Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
    |
    PD-L1 expression • EGFR mutation • EGFR T790M • ALK rearrangement • CD8 expression
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC
    over3years
    [VIRTUAL] Phase I trial of in situ vaccination with autologous CCL21-modified dendritic cells (CCL21-DC) combined with pembrolizumab for advanced NSCLC. (ASCO 2021)
    Secondary objectives include adverse event profiling and determination of drug target activity by immune monitoring studies . This trial, NCT03546361, is currently open for enrollment.
    P1 data • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase)
    |
    PD-L1 expression • EGFR mutation • ALK rearrangement • ALK mutation
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC
    almost4years
    HEMONC CIRM IST Lung: CCL21-Gene Modified Dendritic Cell Vaccine and Pembrolizumab in Treating Patients With Stage IV Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=24, Recruiting, Jonsson Comprehensive Cancer Center | N=36 --> 24 | Trial completion date: Nov 2023 --> Jun 2023 | Trial primary completion date: Nov 2022 --> Jun 2022
    Clinical • Enrollment change • Trial completion date • Trial primary completion date
    |
    PD-L1 (Programmed death ligand 1) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule)
    |
    PD-L1 expression • EGFR mutation • EGFR T790M • ALK rearrangement • CD8 expression
    |
    Keytruda (pembrolizumab) • Ad-CCL21-DC