A CCL21 gene-modified dendritic cell vaccine combined with pembrolizumab in advanced non-small cell lung cancer: a phase I trial
Abstract
Immune checkpoint inhibitors (ICIs) have transformed treatment for non-small cell lung cancer (NSCLC), but resistance to these therapies is common. We report here results from a phase I trial combining intratumoral injection of a CCL21-expressing dendritic cell (CCL21-DC) vaccine with pembrolizumab in patients with advanced non-small cell lung cancer (ClinicalTrials.gov identifier: NCT03546361). The primary objectives were to determine the maximum administered dose (MAD) in the dose escalation phase and the objective response rate (ORR) in the dose expansion. Eleven patients were enrolled in the dose escalation cohort, and 12 patients were treated in the dose expansion cohort at the MAD of 3 ×10 ⁷ cells/injection. The trial did not meet its primary endpoint for ORR as no objective responses were observed, though 36.8% of patients achieved a best response of stable disease. The combination therapy was well tolerated. Post-hoc analyses of longitudinal biopsies revealed that the therapy increased tumor infiltration by CD4+ T cells and novel T cell clones. Disease stability was associated with increased T cell receptor diversity and greater expansion of novel clones following therapy. However, many novel clones failed to persist over time, and immunosuppressive myeloid signaling signatures were identified across time points. Our findings overall demonstrated that CCL21-DC vaccination combined with pembrolizumab can promote T cell infiltration, but this did not translate into meaningful clinical efficacy, potentially due to limited tumor specificity of the T cell response and an inability to fully reprogram the tumor microenvironment.
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BibTeX
@article{oh2026ccl21,
title = {{A CCL21 gene-modified dendritic cell vaccine combined with pembrolizumab in advanced non-small cell lung cancer: a phase I trial}},
author = {Michael S. Oh and Aaron E. Lisberg and Camelia Dumitras and Linh M. Tran and Ramin Salehi-Rad and Kostyantyn Krysan and Raymond J. Lim and Maryam Shabihkhani and Tahmineh Romero and Shuo Li and Weihua Zeng and Zhe Jing and Rui Li and Bitta P. Kahangi and Olga Tsvetkova and Robert D. Suh and Fereidoun Abtin and Scott J. Genshaft and Scott S. Oh and Gregory A. Fishbein and Daniel R. Greenwald and Kanwarpal S. Kahlon and Sidharth R. Anand and Shahryar Ashouri and Jonathan W. Goldman and Jay M. Lee and Xianghong J. Zhou and David A. Elashoff and Edward B. Garon and Bin Liu and Steven M. Dubinett},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78130-7},
url = {https://www.nature.com/articles/s41467-026-78130-7},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A CCL21 gene-modified dendritic cell vaccine combined with pembrolizumab in advanced non-small cell lung cancer: a phase I trial
AU - Michael S. Oh
AU - Aaron E. Lisberg
AU - Camelia Dumitras
AU - Linh M. Tran
AU - Ramin Salehi-Rad
AU - Kostyantyn Krysan
AU - Raymond J. Lim
AU - Maryam Shabihkhani
AU - Tahmineh Romero
AU - Shuo Li
AU - Weihua Zeng
AU - Zhe Jing
AU - Rui Li
AU - Bitta P. Kahangi
AU - Olga Tsvetkova
AU - Robert D. Suh
AU - Fereidoun Abtin
AU - Scott J. Genshaft
AU - Scott S. Oh
AU - Gregory A. Fishbein
AU - Daniel R. Greenwald
AU - Kanwarpal S. Kahlon
AU - Sidharth R. Anand
AU - Shahryar Ashouri
AU - Jonathan W. Goldman
AU - Jay M. Lee
AU - Xianghong J. Zhou
AU - David A. Elashoff
AU - Edward B. Garon
AU - Bin Liu
AU - Steven M. Dubinett
PY - 2026
DA - 2026/10/04
JO - Nature Communications
DO - 10.1038/s41467-026-78130-7
UR - https://www.nature.com/articles/s41467-026-78130-7
AB - Immune checkpoint inhibitors (ICIs) have transformed treatment for non-small cell lung cancer (NSCLC), but resistance to these therapies is common. We report here results from a phase I trial combining intratumoral injection of a CCL21-expressing dendritic cell (CCL21-DC) vaccine with pembrolizumab in patients with advanced non-small cell lung cancer (ClinicalTrials.gov identifier: NCT03546361). The primary objectives were to determine the maximum administered dose (MAD) in the dose escalation phase and the objective response rate (ORR) in the dose expansion. Eleven patients were enrolled in the dose escalation cohort, and 12 patients were treated in the dose expansion cohort at the MAD of 3 ×10 ⁷ cells/injection. The trial did not meet its primary endpoint for ORR as no objective responses were observed, though 36.8% of patients achieved a best response of stable disease. The combination therapy was well tolerated. Post-hoc analyses of longitudinal biopsies revealed that the therapy increased tumor infiltration by CD4+ T cells and novel T cell clones. Disease stability was associated with increased T cell receptor diversity and greater expansion of novel clones following therapy. However, many novel clones failed to persist over time, and immunosuppressive myeloid signaling signatures were identified across time points. Our findings overall demonstrated that CCL21-DC vaccination combined with pembrolizumab can promote T cell infiltration, but this did not translate into meaningful clinical efficacy, potentially due to limited tumor specificity of the T cell response and an inability to fully reprogram the tumor microenvironment.
SN - 2041-1723
ER -